by Andrew Moore
But McLaughlin felt the pawpaw’s greatest potential was not in killing insects and parasites, but in the treatment of cancer. The plant’s Annonaceous acetogenins work by depleting energy in cells—whether insect, worm, or cancer cells—through the inhibition of the cells’ mitochondria. The acetogenins also work in the plasma membrane, preventing cancer cells from growing anaerobically, without oxygen. “So we knock out the cancer cell’s energy production in two ways,” McLaughlin said.
McLaughlin worked with Nature’s Sunshine from 1999 to 2004 and was able to introduce the Paw Paw Cell-Reg, a gelcap supplement taken orally. A clinical study with ninety-four participants showed that the pawpaw extract, containing a mixture of more than fifty acetogenins, is beneficial in a diversity of cancer types. After just four days on pawpaw, a melanoma patient, with lung metastases, could breathe again without the previous “burning” sensation; strength had returned and the patient could ride a bike and walk. Two lipomas had decreased in size, and as an unexpected bonus, a toenail fungus of ten years was diminished. In a breast cancer patient, after seven months of chemo and pawpaw treatment, a tumor almost completely disappeared, and a biopsy after radical mastectomy showed no tumors in fourteen lymph nodes. The patient was cancer-free. In all, McLaughlin reported significant reductions in tumor sizes and tumor antigen levels, with added benefits for treating cold sores, shingles, multiple sclerosis, acne, athlete’s foot, eczema, and psoriasis. The only reported side effect was vomiting—the same effect you would expect after eating too many pawpaws or swallowing a seed. McLaughlin says patients avoid this by reducing dosages.3
McLaughlin’s research showed that the highest levels of Annonaceous acetogenins are present in the tree’s twigs, though the components are also present, in varying amounts, in the tree’s bark, roots, fruit, and, in the least amount, its leaves and wood. The twigs are harvested when they are the most biologically active, and the concentration of acetogenins is highest during the month of May. “The extract is standardized biologically using an invertebrate bioassay, and/or spectrometric instruments,” McLaughlin says. “This is a renewable resource since the trees are not killed during the harvest, and new twigs soon regrow.”
McLaughlin’s work has allowed the plant’s compounds to be harnessed in ways like never before. But pawpaw has been used medicinally for centuries. In 1787, German-born botanist, physician, and zoologist Johan David Schoepf reported, “A wine prepared from the unripe fruit is odorless and is highly useful in children’s sore mouth.” It’s unclear what soreness Schoepf was treating, but McLaughlin also found pawpaws to be effective in treating cold sores. In 1850, medical researchers wrote that “the powdered seeds are used to destroy lice on the heads of children.”4
In 1871, the Journal of Materia Medica published the following: “The fruit of the Popaw is large and fleshy, and after it has been treated with port, yellow, sweet and luscious, and from its taste compared to custard; hence its taste. It is edible and has laxative properties.” The journal went on to say that, domestically, a “saturated tincture of the seeds may be employed for emetic purposes, in doses of a teaspoonful. The bark is a useful tonic in forms of cold infusion.”5 In the 1890s, the Eli Lilly Company actually sold a fluid extract of pawpaw seed as an emetic.6 Anyone who has ever had the misfortune of swallowing even a tiny bit of the seed has an idea of how well this might have worked (for better or worse, I can verify that it works quite well). Describing the practices of those turn-of-the-century doctors, McLaughlin remarks, “The physicians would make you vomit and they would bleed you and they would purge you to get you well. Remember that you sweat just before you vomit. As you sweat you’re sweating the toxins out of your body. And that’s what they believed would help to make you get better—and probably does.”
Other plants in the Annonaceae family are also used medicinally. Extracts of graviola (Annona muricata, also known as soursop, guanabana, and, lately, Brazilian pawpaw) are sold by several companies. A quick Google search reveals well over a dozen companies offering capsules and powdered products, each marketed for its ability to kill cancer cells (McLaughlin says graviola extracts, however, are variously twenty-four to fifty-six times less potent than the pawpaw extracts). In Thailand, extracts of Annona squamosa, A. muricata, A. cherimolia, and A. reticulata are also used to treat head lice. The book Biologically Active Natural Products: Pharmaceuticals reports, “For this, 10 to 15 fresh leaves of A. squamosa L. are finely crushed and mixed with coconut oil, and the mixture is applied uniformly onto the head and washed off after 30 min.”7 A former colleague of McLaughlin’s also reported using the ground seeds of Annona squamosa to treat head lice as a child in India. And yet another member of the Annonaceae family, ylang ylang (Cananga odorata), which is native to the Philippines and Indonesia, is used widely in cosmetics, and its essential oils are used in aromatherapy to address high blood pressure, among other conditions. Its floral scent is used in perfumes, most notably as the principal ingredient of Chanel No. 5.
Pawpaws are also turning out to be highly nutritious. Studies have shown that pawpaws are high in antioxidants, but, as Robert Brannan, current president of the PawPaw Foundation, says, “Finding antioxidants in pawpaw is unremarkable, because they’re a fruit. It’s like saying people have hair.” The question is not just the levels of antioxidants pawpaws possess, but how good they are, and what they do. “And that’s a much tougher question to get at,” he says.
In 1982, a landmark study was conducted on pawpaw nutrition by Neal Peterson, John Cherry, and Joseph Simmons. Because it is a wild fruit, no analysis had been done before. Unfortunately, that study was done not just on the fruit’s pulp, but the skin as well. But we don’t eat the skin, so although the analysis gives us an idea of pawpaw nutrition, it’s not quite accurate. According to Brannan’s research, pawpaw pulp without skin contains about five milligrams of vitamin C per one hundred grams of pulp, which is less than one-third of the value reported in the 1982 study. “So all those numbers that you see for the pawpaw, they’re all wrong,” Brannan says. The 1982 study included skin because the experiment otherwise would have been drastically more expensive. Brannan is planning to conduct a new analysis, but it won’t be cheap. “It’s going to cost upward of ten thousand dollars in order to get it right,” he says, “I am actively working on it right now, but basically what I’m trying to do is get someone to give me a Porsche at a Pontiac price. It’s been slow going.”
Although flawed, the current nutritional data does offer insight as to how nutritious pawpaws might be. The 1982 data shows that pawpaw is high in niacin and protein, as well as several minerals—calcium, phosphorus, magnesium, iron, zinc, copper, and manganese—with amounts far exceeding those of apples, bananas, and oranges. And several essential amino acids were exceptionally high, again, far greater than values found in more popular fruit, including isoleucine, leucine, lysine, phenylalanine, tyrosine, threonine, and valine.8
According to Brannan’s research, we also know that pawpaws are about 75 percent water (“unremarkable for a fruit”); are very low in fat (“I’ve never gotten a fat lipid value of pawpaw that’s been higher than half a percent—basically the only fat that’s in there is the fat that’s needed in the cell membrane”); are low in protein but high in carbohydrates, most of which are sugar; contain a high pH, or acidity level; and are low in fiber. We also know that pawpaw, like red wine, red grapes, cranberries, and chocolate, contains “health-promoting phytochemicals” known as procyanidins. Researchers state that these chemicals have been shown to “have a positive correlation with reduction of coronary heart disease and mortality.”9
However, some research also shows pawpaws could be bad for us. In 1999, researchers investigated a possible link between the consumption of Annona cherimola and A. muricata and an atypical form of Parkinson’s disease (the disease was abnormally frequent in Guadeloupe, where Caparros-Lefebvre and Elbaz conducted the study). They reported that a higher proportion
of patients with atypical parkinsonism consumed A. muricata (97 percent consumed the fruit, and 83 percent took an herbal tea made of its leaves) than patients with Parkinson’s disease (fruit 59 percent; herbal tea 18 percent) or a control group with no Parkinson symptoms (fruit 60 percent; herbal tea 43 percent). It’s significant that 60 percent of the control group ate A. muricata fruit and showed no symptoms, but still, the correlation was strong. Further, younger people who showed symptoms and then stopped consuming Annona products (fruit or tea) were able to reverse their symptoms.10 Yet both fruits—cherimoya (A. cherimola) and soursop (A. muricata), as well as at least a dozen other Annona species—are important food products. “It’s possible that these folks are an island group and they’re just genetically predisposed to get this,” Pomper says. “Because, anecdotally, I know a lot of people who have eaten a lot of pawpaw for years, and they don’t have any symptoms.” And globally, there’s an even larger population that appears to have been safely consuming soursop and cherimoya for centuries.
A 2012 University of Louisville study identified Annonaceous acetogenins as toxic substances that inhibit “critical biological functions.”11 Although the fruit contains far less of these substances than the tree’s twigs and bark, they’re still present (with frozen pulp containing lesser amounts than fresh). At this point, the study’s authors “suggest caution and more study to determine the effects of consumption of these compounds.”
Neal Peterson, however, sees no reason to be alarmed. First, he says, since the toxicity was found in rats when scientists intravenously injected the compounds into them, “this doesn’t prove that [pawpaw] is dangerous to eat, only that it is dangerous to inject as one would heroin.” Neal’s response to the toxicity of pawpaw continues:
For millions of years of evolution, the pawpaw clearly had its seed distributed by mammals that ingested the whole fruit and defecated the seed. We suspect that the primary co-evolved distributors were extinct megafauna (such as mastodons). Whatever species it was, the route of mitochondrial toxicity is so basic that all mammals should be susceptible. Also, more than one mammal species regularly eats pawpaw. Fox, raccoon, bear, and possum consume it. And then Homo sapiens after arriving in North America did so. It is not logical that a severely toxic fruit would be consistently consumed.
Not all pawpaws contain the same amounts of acetogenins; analysis shows some with high levels and others low. “We’re trying to select for low acetogenin too, just because it’s not a good idea to eat something that would be an anticancer compound at a high level,” Pomper says, “I’m selecting for low whenever I can.” But toxicity in foods isn’t unique to pawpaws. Broccoli and other brassicas, for example, contain goitrogens—substances that can suppress thyroid functions and interfere with iodine uptake—as do soybeans, pears, and peaches. Other toxins we commonly consume include lectins (found in grains, legumes, and the nightshade family), hydrazines (mushrooms), opioid peptides (milk, gluten, spinach), phytates and phytic acid (soybeans, wheat, nuts, blackberries, strawberries), and so on. A variety of toxins are filtered and destroyed in our liver and excreted through our kidneys—and this may also occur with acetogenins. But how our bodies react to these compounds is still largely unknown. “At this point, we don’t know a lot about bio-availability [through the gastrointestinal tract], how quickly they’re broken down in the bloodstream,” Pomper says. The Food and Drug Administration, however, considers pawpaw to be safe. “I’ve talked to the FDA,” he says, “and they consider pawpaw a safe food source to eat, and have written me accordingly.”
In a few tangible ways, the work at KSU has paid off. Much of what we know about pawpaws comes from the collaborations between Neal Peterson and KSU researchers—including Brett Callaway, Desmond Layne, Kirk Pomper, and Sheri Crabtree. For the past twenty years, these researchers have published several dozen scholarly articles and presentations on pawpaw—from genetic diversity and geographic differentiation, to seedling rootstock recommendations and behaviors of the pawpaw peduncle borer. Their findings have helped growers like Maryland’s Jim Davis understand the culture of growing pawpaws, and the literature coming out of KSU undoubtedly contributes to his success (not to mention that of the countless others who have reached out for answers to basic questions, and requests for seed and trees). But closer to home, there’s another testament to KSU’s success, a more basic and visual marker. For any other fruit, this example would seem insignificant, but when considering the pawpaw, it is absolutely a big deal: in Lexington, Kentucky, a local farmer’s pawpaws are sold at a grocery store.
When Ilze Sillers bought her Woodford County farm twenty years ago, she could have planted anything. “It had a tobacco base, but I knew I did not want to grow tobacco, for personal reasons, health reasons, and that tobacco was, as a crop, facing extinction,” Ilze recalls. She attended a Third Thursday program at KSU, a monthly workshop used to showcase new or uncommon sustainable agricultural ventures. “I happened to go to the workshop on pawpaws, and I thought, this is absolutely perfect,” she says. “They’re native to the area, they don’t require pesticides, there seems to be an interest in the market for them, no one’s doing it, and so I just got very interested.” So Ilze planted pawpaws—three hundred of them.
Ilze was not the only small farmer in Kentucky moving away from tobacco. As an economic analysis published by the University of Kentucky states, “As those living in rural Kentucky look forward to the 21st century, it is becoming increasingly clear that the economic environment will continue to change radically. The future of tobacco, long the leading cash crop for the farmers in the Commonwealth, looks increasingly bleak, as federal officials renew efforts to further regulate the sale and use of tobacco products.”12 No doubt, growing tobacco is a strong cultural tradition in Kentucky, and if it disappears part of the culture disappears. But tobacco is not the only tradition.
As I’ve mentioned, Kentucky’s original inhabitants ate and cultivated pawpaws; they wove clothing and crafted tools and nets from the tree’s inner bark. Daniel Boone and the region’s other settlers ate them. In 1828, botanist Charles Wilkins Short wrote that portions of Kentucky were “once the paradise of papaws, where immense orchards of large trees were everywhere met with.”13 In the late nineteenth and early twentieth centuries, newspapers reported on the wild pawpaw crop: “Pawpaws plentiful,” noted Louisville’s Courier-Journal in 1882,14 and the Lancaster Central Record, in 1901, said, “Pawpaws have appeared on the market, and are said to be plentiful.”15 Pawpaws were the subject of poems, and, serving another form of inspiration, made into beer. In 1896, the Courier-Journal remarked, “A pint of it will take the paint off a brick house and make a man forget he has a mother-in-law.”16 Children made hats from pawpaw leaves, and a pawpaw whistle, crafted from the tree’s bark, was once a widespread novelty.
Later, when the fruit began to fade from the broader American consciousness, many folks in Kentucky just kept on harvesting and eating. So when KSU decided to introduce the fruit as a potential replacement for tobacco, it seemed like a logical fit. “Rather than introduce something from another country that may not do well in the climate,” Desmond Layne recalls, “it was something that was already available in certain farmers markets, and people in rural areas were familiar with it.”
Growing pawpaws would be more sustainable and better for the environment than tobacco. Historically, tobacco cultivation has relied on fumigating with pesticides and herbicides. The crop has also been plagued by viruses, and in general growing tobacco is a very intensive system requiring numerous inputs. “The nice thing about [a pawpaw] orchard is that once the trees are planted and they’ve come into production, they are perennial, they are there for as long as those trees live,” Layne says. Further, growing a fruit versus a toxin offers peace of mind to the farmer. “It’s one thing to provide people with food, it’s another thing to provide them with something that can kill them,” Layne says. “I’m not castigating people who grow tobac
co, because it’s been a part of the nation’s history since Native Americans were growing tobacco and trading it with the explorers that were coming over from Europe. But certainly, if I have the choice to grow other things that are going to also provide me with profitable income, I would much rather be growing food.”
When choosing pawpaws as her crop, Ilze Sillers agreed. KSU connected Ilze with Oregon’s Northwoods Nursery for grafted cultivars, including selections from KSU’s germplasm collection as well as Neal Peterson’s advanced selections (a few years before they were named and released). When they started to produce fruit, “it just was gangbusters for several years,” Ilze says. She sold at the county farmers market as well as to restaurants, and she developed a relationship with Lexington’s Good Foods Co-op. Each year, Good Foods buys more than a thousand pounds of pawpaws, approximately half of Ilze’s crop, and sells each and every piece of fruit. Last year, Ilze sold another thousand pounds of pawpaws to a second buyer, Wildside Winery. What started as an idea—that pawpaws might be a niche crop for Kentucky’s small farmers—is now being tested by folks like Ilze Sillers. So far, with a bit of effort, ingenuity, and salesmanship, it seems to be working.
There have been many great presentations during the conference, but when we’re finally able to tour the orchard, it’s what we’ve all been waiting for. The alpha orchard, growing to the right of the small road that leads to the orchard, is the original collection planted by Brett Callaway. Beyond it, a long orchard makes up the germplasm repository. This collection was started by Desmond Layne and continued through Pomper’s work at KSU. Typically, visitors are asked to refrain from picking up fruit, since the program uses the pawpaw for ongoing research. But at this point in the season, they’ve collected their information, and we’re given the green light. One observer describes the scene as looking like “a group of children on an Easter egg hunt.”17 We break into the mango-sized fruits, perfectly ripe, and some of us fill bags to take home. But with the Pawpaw Extravaganza Dinner awaiting, we’re careful not to eat too much.