O nce again, just in time for Thanksgiving, millions of people have been told their romaine lettuce might be contaminated with a toxic strain of E. coli bacteria, that it’s potentially deadly, and that they should throw it away immediately and sanitize the fresh-produce drawer of their refrigerator.

No one knows why this is happening, exactly. There are inferences, speculation and intriguing clues, but the best minds of the U.S. government, the lettuce-growing states of California and Arizona, and the leafy greens industry have failed to figure out why romaine keeps getting contaminated — or how they can stop it from happening again and again.

Last year the warning from the U.S. Centers for Disease Control and Prevention came on Nov. 20, two days before Thanksgiving, and was unusually sweeping, declaring that no romaine in the United States could be assumed safe to eat — and all of it should be discarded. This year the warning came Nov. 22, six days before the holiday. It said 40 people in 16 states had been sickened, most of them hospitalized after consuming romaine grown in or near Salinas, Calif., and contaminated with a Shiga-toxin-producing E. coli strain called O157:H7 that can lead to kidney failure and is potentially lethal.

The numbers jumped again Tuesday, when the CDC reported that 67 people in 19 states have been sickened.

“It’s heartbreaking and frustrating,” said Dan Sutton, a lettuce grower in San Luis Obispo, Calif. “We will have to change how we farm leafy greens.”

The bulk of the romaine sold in the United States comes from just two growing areas: the Salinas Valley of California (harvested in late spring, summer and fall) and the Yuma, Ariz., growing region that includes the Imperial and Coachella valleys of Southern California (winter and early spring).

Contaminated agricultural water is a prime suspect in these outbreaks. The Trump administration delayed implementation of new agricultural water testing rules, developed during the Obama administration, that were set to take effect last year.

The rules would require farmers to test four times per growing season for generic E. coli in agricultural water. Some farmers pushed back against the new rule, calling it confusing and unwieldy. The FDA decided to delay implementation. Now, large farms will be required to meet the requirements in January 2022, with small farms following in 2023 and very small farms in 2024.

But leafy greens industry officials say the delay in the rule isn’t to blame for the romaine lettuce outbreak, because the industry already performs the water tests on a monthly basis.

Still, the growers said they are frustrated that their own standards to prevent contamination — codified in the California Leafy Greens Marketing Agreement — have not resolved the problem.

“They are the most stringent and most scientifically based requirements on how to grow leafy greens,” said Sutton, who is also chairman of the marketing agreement.

After last year’s outbreak, the FDA determined the E. coli strain that sickened people across the country came from surface water rather than ground water pumped from an aquifer. As a result, the coalition of leafy green growers decided to ban the use of surface water unless it is treated with anti-bacterial chemicals 21 days before harvest.

Scott Horsfall, CEO of the marketing agreement, said that gives the chemicals plenty of time to kill off E. coli and other pathogens.

“The FDA believes [the bacteria] dies off after four or five days,” Horsfall said. “We went to 21 days to be conservative.”

The coalition created its first industry standards to prevent pathogen contamination in 2007, a year after nearly 200 people became ill after eating spinach contaminated with E. coli. Nearly half were hospitalized, 31 developed kidney failure and three people died.

With outbreaks continuing, the industry took further measures, requiring farther setbacks of septic tanks from agricultural fields, and tripling the buffer between livestock, which can carry E. coli, and leafy greens operations from 400 to 1,200 feet.

But whatever has been done so far has not fixed the problem — and the experts are still searching for a theory of the case.

“This has been devastating for the growers. They have investigated so many resources and made so many changes to keep this from happening,” said Sonia Salas, assistant vice president for food safety for Western Growers, a trade group for produce growers in four western states.

Investigators are looking at other variables that might make romaine particularly vulnerable, including whether the very structure of the funnel-shaped lettuce is playing a role in harboring the pathogen.

The timing of the E.coli outbreaks is striking: They have often occurred late in the growing season for a given region, when crops are being rotated. That has drawn attention of experts who are searching for some common environmental explanation for the recurring outbreaks.

Trevor Suslow, vice president of produce safety for the Produce Marketing Association, said the season for romaine lettuce ends in the fall in the Salinas Valley. That’s just weeks after neighboring fields are often prepped with manure or composting materials for spring crops.

The possibility of E.coli drifting to the lettuce fields — through water or wind or other means — is an “absolute current focus right now to determine why these seasonal outbreaks have been happening.”

Suslow said the weather can exacerbate problems with the contamination. “This is all happening at a time when water temperatures and humidity is high,” he said. “Those things are shown to favor survival and persistence of bacteria.”

There are other seasonal factors that could be contributing to the problem. Michele Jay-Russell, a microbiologist and manager of the Western Center for Food Safety at the University of California at Davis, said cattle, deer, goats and feral pigs carry E. coli O157:H7.

“It’s just a natural bacteria for them; they pass it through their feces,” she said. “In cattle we tend to see a particular seasonality to it. In the fall some can become super shedders. We aren’t sure why there are these seasonal spikes.”

An outbreak in the spring of 2018, which sickened 210 people and killed five, may have involved contaminated irrigation water from a canal that ran adjacent to a sprawling feedlot for cattle near Yuma, although investigators never definitively proved the chain of contamination. A 2017 outbreak that killed one person and sickened 25 in the United States and Canada has been loosely linked to California and Arizona growing areas.

After the November 2018 outbreak, the FDA traced the contamination to three counties in California. The investigation found the outbreak strain of E. coli in sediments in an open reservoir on one farm in Santa Barbara County, but the FDA said there was “insufficient evidence to conclude that this farm was the sole source of the outbreak.”

The farm did have a system in place for testing water for E. coli and sanitizing it before use, but the FDA investigation showed it was not foolproof.

“Inspection of water tank sanitizer treatment systems used in harvest/postharvest handling revealed that some units had undissolved sanitizer cakes and that some tank systems were constructed in a manner that likely did not allow for optimal sanitizer treatment of the agricultural water before use,” the FDA reported. “Additionally, untreated water from the contaminated reservoir was used to fill tank trucks which broadly sprayed water on roads for dust abatement and these roads were traveled on by harvest equipment prior to commencing harvest operations.”

“E. coli can live in water sediments for years,” said Frederick M. Cohan, a microbial ecologist at Wesleyan University. “What you want to do is keep it from getting in there in the first place.”

The virulent strain of E. coli at the center of this latest leafy green outbreak is the same pathogen that in 1993 killed four children and left 171 people with permanent injuries, including brain damage and kidney failure. The infamous outbreak was linked to undercooked Jack in the Box hamburgers.

With meat, grilling, baking or frying it at high temperatures typically kills the pathogens. High heat is typically not used to make salads.

“Most people don’t cook lettuce,” CDC spokesman Brian Katzowitz said. “There’s no kill step for that. That safety net of cooking is not there.”

The FDA said consumers can still safely eat romaine from outside four Salinas-area counties — Monterey, Santa Clara, Santa Cruz and San Benito as well as hydroponically grown lettuce. In a statement on Friday, Frank Yiannas, the FDA deputy commissioner for food policy and response, said improvements in labeling and tracking made it possible to trace the contamination back to a single region — in contrast with what happened last year, when the FDA told consumers to throw away any and all romaine regardless of its source.

This new investigation, Yiannas said, “reinforces our recommendations that we have made to the leafy green industry: Producers must continue to review their practices and all segments of the supply chain must improve traceability to enhance food safety.