It takes gumption to cold-call the co-discoverer of the DNA double helix and ask him if he’d be willing to take a look at the anti-cancer potential of a food-derived natural product.

David Wales and Rick Jahnke, the co-founders of American BioSciences, did just that back in August 2009, when they emailed James Watson, chancellor of the esteemed Cold Spring Harbor Laboratory, and asked him to consider data showing that their company’s fermented wheat germ extract (FWGE) could modulate cancer metabolism in ways that inhibited cell proliferation.

Watson, who died on November 6 at age 97, was impressed by what he saw. Without hesitation, the legendary and controversial Nobel Prize winner invited Wales and Jahnke to the lab to begin a research collaboration that led not only to published papers, but to a friendship that gave these natural products execs a rare glimpse into the mind and life of a brilliant, contentious man whose impact on science and culture is hard to overestimate.

“It was like meeting the Wizard of Oz,” recalls Wales of his first meeting with “Jim,” as Watson preferred to be called. “He was a brilliant, brilliant guy. He seemed to know everything.”

Watson had a reputation for being difficult, confrontative, and not inclined to spend time or attention with people he considered beneath him. But, after considering the quality and depth of the research Jahnke and Wales had sponsored on a shoestring budget, Watson took a shine to the pair.

“A lot of people didn’t like him, but Rick and I got on very well with him,” says Wales, who first read Watson’s The Double Helix, when he was in college. He never dreamed he would one day share dinners with its author.

What was it that prompted a scientist of Watson’s stature to give even a minute’s time to early-stage research on a wheat germ extract?

Two things: first, Watson was deeply interested in the molecular mechanics of cancer, and FWGE contained phytochemicals that could move cancer cell metabolism away from glycolysis and toward oxidative phosphorylation. Second, the data Wales and Jahnke presented came with a posthumous “recommendation” of sorts, from one of Watson’s old friends and mentors, Hungarian biochemist Albert Szent-Györgyi.

A Shift in Perspective

James Watson is rightly regarded as a progenitor of modern medical genetics, especially as applied to cancer care. He was one of the first ‘field marshals’ in Nixon’s War on Cancer, and an advisor to the National Cancer Institute throughout the 1970s. As head of the Human Genome Project from 1990-1992, he was a main driver in the effort to decode the genes and mutations that underlie neoplasia and malignancy.

But by the turn of the millennium, Watson recognized that from the perspective of clinical cancer care, the research community’s obsession with genes was leading nowhere.

“I fear we still do not yet have in hand the ‘miracle drugs’ that, acting alone or in combination, would stop most metastatic cancer cells in their tracks. To develop them, we may have to turn our main research focus away from decoding the genetic instructions behind cancer and toward understanding the chemical reactions within cancer cells,” he wrote, in a brief but impactful 2009 New York Times op-ed called, “To Fight Cancer, Know the Enemy.”

In it, he called for a shift away from chasing genes, and toward what we now call metabolomics. Knowledge of genes alone had not—and would not—yield significant therapeutic progress without an equally thorough understanding of how cancer cells behave metabolically, he argued.

By the turn of the millennium, Watson recognized that from the perspective of clinical cancer care, the research community’s obsession with genes was leading nowhere.

“After my colleagues and I discovered the double helix of DNA, biology’s top dogs then became its molecular biologists, whose primary role was finding out how the information encoded by DNA sequences was used to make the nucleic acid and protein components of cells,” Watson wrote. “Clever biochemists must again come to the fore to help us understand the cancer cell chemically as well as we do genetically.”

It was this Times editorial that prompted Wales and Jahnke’s bold cold-call.

Szent-Györgyi’s Legacy

Watson was willing to look at the FWGE data because it emerged from the legacy of his old friend Dr. Szent-Györgyi, and because it pointed precisely in the direction he thought cancer research ought to be heading.

When Watson befriended Szent-Györgyi in the late 1940s, the latter was already an older man, widely respected for his work isolating Vitamin C (which, in his time, was called Hexuronic acid) and for describing the citric acid cycle. Szent-Györgyi won a Nobel Prize in 1937. (Notably, in 1940, he donated all the prize money to support Finnish soldiers and Hungarian volunteers fighting off the Soviet invasion of Finland). 

In 1947, Szent-Györgyi emigrated to the US, and established the Institute for Muscle Research at the Marine Biological Laboratory in Woods Hole, MA.  This is where a young James Watson, fresh off the groundbreaking double helix discovery, met and befriended the elder researcher. In fact, Watson wrote the first draft of The Double Helix at Szent-Györgyi’s house on Cape Cod.

Szent-Györgyi had a longstanding interest in cancer biology, in part because the disease took the lives of his beloved wife Marta, and their daughter, Cornelia. He believed the key to understanding cancer—and thereby treating it—was in the Warburg Effect. As Otto Warburg observed in the 1920s, most cancer cells regardless of type, show a distinct metabolic characteristic: they preferentially generate energy via glycolysis and lactic acid fermentation, rather than by oxidative phosphorylation (OxPhos) typical of normal non-neoplastic cells.

Watson was well-versed in much of Szent-Györgyi’s work. But he was completely unaware of his fermented wheat germ extract research. On hearing it, he became immediately excited.

Warburg’s observations sparked Szent-Györgyi’s quest for compounds with potential to shift cell metabolism toward OxPhos.

In 1983, three years before his death, Szent-Györgyi published a paper in describing certain benzoquinones in wheat germ that showed notable anti-neoplastic properties against Erlich ascites cells, especially when combined with ascorbates. This effect was not the “classic” cell-obliterating cytotoxicity seen with chemotherapy drugs. It was, as Szent-Györgyi described it, a change in cellular metabolism leading to “an inability of the treated cells to replicate, rather than in their being destroyed directly.” It was precisely the sort of shift he’d been seeking.

Multiple Mechanisms

Szent-Györgyi did not live long enough to delve further, and his observations might have gone nowhere, had it not been for Máté Hidvégi, PhD, another Hungarian researcher who picked up the inquiry where Szent-Györgyi left off.

Hidvégi and others isolated, refined, and standardized the quinones initially identified by Szent-Györgyi, and then tested the concentrated extract against a wide range of human cancer types, including lymphomas, colorectal cancers, and melanoma. They clarified key mechanisms by which these compounds modulate cancer metabolism. Among them:

• Dose-dependent restriction of cancer cell glucose uptake by limiting the activity of an enzyme called glucose-6-phosphate dehydrogenase [G-6-PDH]

• Inhibition of transketolase (TK), an essential catalytic enzyme in the glycolytic reactions through which cancer cells produce ribose from glucose-derived carbons. TK is a key player in glycolysis, aka “Warburg metabolism,” and it is necessary for cancer proliferation. Restriction of the TK-dependent pathway by FWGE quinones pushes metabolism back toward OxPhos, limiting proliferation.

• Promotion of cancer cell apoptosis by downregulating PARP, a key enzyme for DNA repair.

• Reduction in number of MHC-1 molecules on tumor cell surfaces, rendering them more vulnerable to recognition and attack by natural killer cells.

• Raising levels of intercellular adhesion molecule-1 (ICAM-1) within tumor vasculature, facilitating entry of immune system cells into tumor tissue.

• Potentiation of Tumor Necrosis Factor (TNF)-α.

• Inhibition of ribonucleotide reductase (RR), which converts ribonucleotides to deoxyribonucleoside triphosphates—the precursors of DNA synthesis.

• Inhibition of potentially cancer-promoting cyclooxygenase (COX) molecules.

Meaningful Clinical Impact

These observations are not just scientific curiosities; they translate into meaningful clinical impacts.

A Phase III open-label clinical trial published in 2003 showed that the concentrated FWGE extract—known by the brand name Avemar—reduced the odds of colorectal cancer recurrence, minimized metastases, and improved survival when used for six months, in combination with radiotherapy and other conventional oncologic protocols. The study involved 170 patients, all of whom had undergone prior removal of primary tumors, and were undergoing some form of chemotherapy, radiation, or both. The patients were offered the choice of adding Avemar (available as an OTC product), 9 g/day to their regimens. Of the total cohort, 66 (39%) opted to take Avemar.

An earlier study of 42 patients with Stage III melanoma showed that when combined with dacarbazine (DTIC), Avemar markedly improved progression-free one-year survival compared with DTIC alone (55% vs 39%). At the 12-month mark, 36% of those in the combination group showed melanoma progression, versus in 75% of the DTIC monotherapy group.

A 7-year follow-up of these patients showed that those who received only dacarbazine survived a mean of 44.7 months, whereas those who received dacarbazine with Avemar survived a mean of 66.2 months–a 50% increase in overall survival time. Furthermore, whereas 11% of those receiving dacarbazine alone experienced severe side effects from chemotherapy, none of those on dacarbazine with Avemar suffered severe side effects.

There’s also evidence that addition of Avemar to standard protocols could reduce recurrence and progression of oral squamous cell carcinoma. The study involved 43 patients treated with conventional therapies alone or conventional care plus Avemar for 12 months. The recurrence rate was 4.5% in the Avemar combo group, versus 57% with conventional care alone. The disease progression rate was 9% for conventional care plus Avemar, versus 62% for conventional care alone.

Throughout these and other studies, FWGE has proven itself very safe and generally well-tolerated. It shows a strong selectivity for cancer cells while sparing normal tissue. The levels that affect cancer cell metabolism are 50 times lower than the levels that might impact metabolism in normal non-cancer cells. The most common adverse effect is the unpleasant taste of the product, which is taken as a powder mixed with water.

High Praise

Wales recalls that during his first meeting at Cold Spring Harbor, it was clear that James Watson was well-versed in much of Szent-Györgyi’s work. But he was completely unaware of the FWGE research. On hearing it, he became immediately excited. He believed the Avemar studies had scientific integrity, and that the mechanisms they described were biochemically sound.

“It was very exciting because he validated everything we presented. There was not one point on which he said, ‘No, no! That doesn’t make sense.’ In typical Watson fashion he said right then and there, ‘Would you guys like to present to the entire lab?’ We weren’t prepared for that, but Watson just walked into this room where all the lab leaders were meeting, and he interrupted them. We made the presentation, and they loved it.”

That’s very high praise, given Watson’s stature and the reputation of the Cold Spring Harbor Lab. Before that day was out, Jahnke and Wales had an invitation to collaborate.

“It was very exciting because he validated everything we presented. There was not one point on which he said, ‘No, no! That doesn’t make sense.'”

David Wales, co-founder, American Bioscences

The team at American Biosciences had worked closely with Dr. Hidvégi to bring Avemar to market in the US. Guided by Watson and the Cold Spring Harbor team, the company further refined the product by identifying and isolating the most biologically active fractions within it. In so doing, they could greatly minimize the effective dose, which improves its tolerability and ease of use. Moreover, they were able to eliminate the gluten naturally present in wheat germ, rendering the product entirely gluten-free.

This super-concentrated, gluten-free formulation is called Metatrol.  

The collaboration between Watson’s team, Dr. Hidvégi, and scientists from American Biosciences also resulted in identification of another important mechanism by which FWGE alters cancer cell biology. They showed it could inhibit melanoma cell growth by 68%, by increasing mitochondrial release of cytochrome c. This signaling molecule is key in inducing apoptosis. Highly malignant cancer types, like melanoma, are adept in suppressing cytochrome c production.

They also found that exposure to FWGE quinones increased carbon flux into cancer cell mitochondria, revving up the Krebs cycle, and promoting OxPhos. Published in 2020, this was among James Watson’s last major papers.

A Love of Tennis & Cars

Not surprisingly, Watson had a reputation for being very serious about his work, and very demanding of the people working under him. But he was by no means an “all work, no play” ogre.

Wales and Jahnke recall that Watson liked to gather his research teams for after-hours drinks and dinner at one of Cold Spring Harbor’s taverns. “He had this reputation for being antisocial, but he really encouraged everybody to get together at the end of the day, and have a drink or two, to talk and socialize.” Wales told Holistic Primary Care.

Watson also had a thing for sports cars. Even into his 90s, could be spotted driving his Jaguar around the Cold Spring Harbor campus, sometimes at breakneck speeds.

“We were in one of the last acts of his scientific career. Dr. Watson gave us the opportunity to validate the research on FWGE and to transform the product. Even though he made a massive discovery decades ago, he didn’t stay put. He didn’t say, ‘OK, I did something great and now I can just move to the Bahamas and live on a yacht.’ He never stopped.”

–David Wales, American Biosciences

And he was a big tennis fan, an interest that Jahnke shared. This led to a special connection between the two.

“Being a business school guy with no scientific background whatsoever, there wasn’t much I could really talk to him about, except that we both loved tennis,” Jahnke tells Holistic Primary Care. “So, we would talk tennis all the time. I went to the US Open with him, and we spent the entire day together having a great time. That’s where I got to know him, and became friendly with him.

Jahnke was aware of Watson’s 2007 book, Avoid Boring People: Lessons from a Life in Science. On the ride home from the US Open, Jahnke quipped that it must’ve been tough for Watson, who “got stuck with me—a boring business guy–for 14 hours. And he said, ‘Well, you’re not that boring.’”

Watson’s Shadow

James Watson—like many White males of his generation—held racist and sexist attitudes which he made little effort to hide or change. Along with his personal arrogance, these plagued him throughout his career.

He held there were inherent biological differences between peoples of European and African ancestry, and that these traits translated into differences in intelligence and ability to reason. He also held that there’s something in melanin that confers stronger libido on darker skinned people. “That’s why you have Latin Lovers,” he’s quoted as saying. “You’ve never heard of an English Lover.”  And he’s on record stating that thin people are inherently more ambitious than fat people.

These views provoked widespread criticism from many scientists, and from the general public alike, and ultimately cost him his chancellorship at Cold Spring Harbor.

But the backlash did little to change his perspectives. In 2019, shortly after he was forced to step down from leadership at Cold Spring Harbor, he stated that his views on race and intelligence had not fundamentally changed.

“I would like for them to have changed, that there be new knowledge which says your nurture is much more important than nature. But I haven’t seen any knowledge. And there’s a difference on the average between blacks and whites on IQ tests. I would say the difference is, it’s genetic.”

In reality, many researchers have published work contesting the genetic basis of race. Watson, it seems, chose to ignore or dismiss these papers.

Watson also held that there were fundamental biological differences between women and men that resulted in differences in aptitude and achievement, especially in the sciences.

In The Double Helix, first published in 1968, he is patronizing and dismissive of Rosalind Franklin, a young researcher whose X-ray crystallography provided key clues to DNA’s structure, but who was not properly credited for it during her lifetime. Referring to her as “Rosy”—a nickname she never used and considered an affront—and calling her “shrewish” and “belligerent,” Watson also justified the use of her work without consent, on the ground that she would never have derived DNA’s helical form on her own.

A 1980 edition of The Double Helix included an epilogue in which Watson apologized for his earlier negative portrayals of Franklin, admitting that he was wrong in his assessment of her character and scientific acumen.

In the 1950s, Franklin was working for Maurice Wilkins at Kings College, London, with whom she had a poor collegial relationship owing to Wilkins’ disparaging attitudes toward women (it was Wilkins who first took to calling her, “Rosy”). Franklin had only met Watson and his colleague Francis Crick a few times, and they never worked together directly. Historians contend that it was Wilkins who brought the groundbreaking “Photo 51”—made by Franklin’s student Raymond Gosling under her aegis–to Watson and Crick without Franklin’s or Gosling’s knowledge or consent.

Watson, Crick, and Wilkins received the Nobel Prize for their DNA discoveries, based in part on Franklin and Gosling’s work. Franklin—who died of ovarian cancer in 1958—was not credited in the Nobel, nor was Gosling. Their contributions were only formally acknowledged decades later.

Complexity & Contradiction

Wales and Jahnke say they were well aware of Watson’s racism and sexism, and they stressed that they in no way share those views. Neither are they inclined to explain them away or minimize the pernicious impact of Watson’s bigotry.

But in their experience, Watson was not the malicious, eugenics-minded White supremacist that many of his critics portray him to be. Rather, they saw him as a socially-inept, politically tone-deaf man convinced of his own brilliance, stuck in archaic ideas, and fond of taking provocative stances.

“Politically, he was actually very liberal,” recalls Wales. “I’d say he was uber-progressive.”

Watson was among 22 Nobel laureates to sign the 2003 Humanist Manifesto. Despite his aforementioned views on genetics and race, he strongly supported Barack Obama’s presidency, and backed Bernie Sanders’ 2016 bid for the Oval Office. 

He vehemently opposed the idea of patenting human genes –a stance that prompted him to resign from the Human Genome Project once the NIH made clear that it wanted to pursue patents on particular DNA sequences. He firmly believed that the Project should operate under the requirement that any and all discoveries be made public within 24 hours, to prevent them from falling prey to private monopolies.

In the 4-year battle over Myriad Genetics’ attempt to patent the BRCA1 and 2 genes, Watson filed an amicus curiae brief with the Supreme Court, arguing against the company, stating that “Life’s instructions ought not be controlled by legal monopolies.”

At the same time, Watson was equally strong in his belief that if genetic testing and gene-based therapies could detect and cure human diseases, they ought to be widely deployed to do so. In his view, this included screening for birth defects and—should it ever become possible—use of genetic engineering to enhance human intelligence.

If that perspective has a whiff of eugenics, keep in mind that Watson was, himself, the parent of a child diagnosed with schizophrenia. Throughout his career, he was open about the plight of his son Rufus, and expressed hope that genetic research could ultimately shed light on the causes of this and other serious mental illnesses.  

An Equal Opportunity Antagonist

For what it’s worth, James Watson was an equal opportunity antagonist. In his books, he variously describes scientific colleagues as “dinosaurs”, “deadbeats”, “fossils”, and “has-beens.”

His less-than-flattering portrayals of Francis Crick in The Double Helix –a book that overflows with as much gossip and personal drama as scientific data–caused a serious rift between the two that lasted for years.

He had particular animus for J. Craig Venter, himself a controversial figure, who started his genetics career at NIH, but left the Human Genome Project, founded the private sector Celera Genomics, and raced NIH to an uneasy tie in the quest to sequence the entire human genome.

Venter and Watson had much in common, including unshakable confidence in their own intelligence, faith in science, top-down leadership style, and allegations of sexism. But they differed strongly on the issue of gene patents, Watson advocating for the public domain while Venter championed the private sector and corporate enterprise.

During the heated competition between Celera and the Human Genome Project, Watson referred to Venter as “Hitler,” adding that the fruit fly genome—which Celera aimed to sequence before taking on the human genome—was Venter’s “Poland.”

Wales and Jahnke do not gloss over any of Watson’s shadows. But in sharing dinners with him and his wife, Elizabeth, or going out with him and his research teams, they also got to know other sides of the man—his lightheartedness, his humor, his feelings for family.

“He Didn’t Stay Put”

Jahnke recalls that Watson expressed great concern about the wellbeing of his son, and fretted over Rufus’ struggles with schizophrenia. “He was very worried about his child. I remember him saying, ‘If your kids are unhappy, do everything you can to get them into a happier situation. Don’t let it linger.’ That really stuck with me, in relation to my own my kids.”

Though he headed some of the world’s biggest scientific institutions, Jim Watson always considered himself an outsider, and an iconoclast who relished opportunities to challenge establishments. Perhaps it was that renegade streak that prompted him to take two unknown natural products entrepreneurs under his wing.

Wales and Jahnke had no prestigious scientific credentials or academic positions. They came to Watson as true outsiders to the biomedical research establishment. But they had good scientific instincts, they knew what they were talking about, and they impressed Watson with the work they had sponsored.

Wales says what he admired most about Watson was his unceasing curiosity and willingness to continue pursuing questions that interested him with vigor and enthusiasm.

“We were in one of the last acts of his scientific career. And Dr. Watson gave us the opportunity to validate the research on FWGE and to transform the product. Even though he made a massive discovery decades ago, he didn’t stay put. He didn’t say, ‘OK, I did something great and now I can just move to the Bahamas and live on a yacht.’ He never stopped, and that’s the coolest part about him.”

END