In recent years, numerous studies have revealed that tumors contain a diverse range of bacteria, fungi, and viruses. These unexpected findings have prompted scientists to reconsider their understanding of cancer. The implications of these discoveries are exciting: Could tumors release specific microbes into the bloodstream as an early indicator of the disease? Can antibiotics play a role in shrinking tumors?
A start-up capitalized on these findings in 2019 and began developing microbe-based cancer tests. This year, regulators prioritized the company’s upcoming trial due to its potential to save lives. However, multiple research teams have now challenged three prominent studies in the field, claiming an inability to replicate the results. The critics argue that the supposed tumor microbes were likely non-existent or a result of contamination.
Steven Salzberg, an expert in DNA sequence analysis at Johns Hopkins University, published one of the recent critiques, stating, “They just found stuff that wasn’t there.” Despite this, the original study authors defended their data and highlighted more recent studies supporting their conclusions. This ongoing debate highlights the challenges of deciphering the true nature of tumor microbes, while also showcasing the potential these discoveries hold.
Biologists have long known that microbes play a role in cancer development. For example, the human papillomavirus (HPV) causes cervical cancer by infecting cells, and certain bacteria strains contribute to other types of cancer in organs such as the intestines and stomach. Advances in technology, specifically DNA analysis techniques, have accelerated the discovery process. Researchers can now extract DNA fragments from tumors and determine whether they originate from human cells or other species.
In 2019, scientists at New York University School of Medicine published a groundbreaking study in Nature that focused on pancreatic cancer. They identified DNA fragments from various fungal species in many tumors and concluded that these fungi drove tumor growth. This study caught the attention of Dr. Peter Allen at Duke University School of Medicine, who subsequently searched for microbes in pancreatic tumors from his patients. However, after analyzing 140 tumors, Dr. Allen and his team couldn’t find significant amounts of microbial DNA, including fungi. They also found a lack of fungal DNA in the original study data. These findings were published in Nature in August.
Nevertheless, the New York University researchers stood by their work and pointed to other data supporting their results. In August, Tokyo Medical and Dental University researchers reported finding fungi in pancreatic tumors of 78 out of 180 patients. Additionally, patients with fungal-containing tumors had a higher risk of post-surgery mortality.
Another study under scrutiny is a 2020 report in Science by a team from the Weizmann Institute of Science in Israel. The study, which examined 1,500 tumors from seven cancer types, discovered distinct sets of bacteria in each tumor type, with breast cancer exhibiting significant microbial diversity. However, microbiologist Jacques Neefjes and his Leiden University colleagues failed to detect bacteria inside cancer cells in their own collection of 129 breast cancer samples. They published their findings in January, asserting that the bacteria found in the Weizmann study were byproducts of infections and not a normal component of breast cancer tumors. The Weizmann team leader, Ravid Straussman, disputed these claims and maintained the presence of bacteria in cancer cells.
The third study, published in Nature in 2020, involved researchers from the University of California, San Diego. They analyzed a tumor DNA database and trained a computer to identify microbial DNA sequences in 18,000 tumors. The computer successfully recognized 33 cancer types based on their unique combinations of microbes. However, when researchers examined the microbes associated with specific cancers closely, they seemed out of place. For instance, adrenal gland tumors appeared to contain a virus that typically infects shrimp in the Gulf of Mexico, and bladder cancer seemed to favor bacteria known to grow on seaweed. Researchers deemed these discoveries nonsensical and questioned the accuracy of the study.
Dr. Abraham Gihawi, a postdoctoral researcher at the University of East Anglia, reanalyzed the data alongside Dr. Salzberg, leading them to conclude that the study was erroneous. Dr. Gihawi and his colleagues published their findings in the journal Microbial Genomics. However, Dr. Knight, the San Diego team leader, defended their work, stating that they employed the best resources available and improved their methods in subsequent papers.
Despite the criticisms, Micronoma, a company co-founded by Dr. Knight in 2019, continues to develop cancer tests based on microbe findings. The company has raised $17.5 million in investments and received the FDA’s “Breakthrough Device” designation for a lung cancer test. Micronoma’s CEO, Dr. Sandrine Miller-Montgomery, confirmed that the recent critiques haven’t affected the company’s plans.
While some experts like Dr. Sven Borchmann of the University of Cologne question the rush to turn findings into medical tests without further experimentation, others believe that certain microbial species uncovered in these studies still hold validity. Qin Ma, a computational biologist at Ohio State University, emphasizes that despite the recent challenges, the weight of evidence gathered over the years supports the presence and importance of microbes in tumors. The controversy surrounding these studies exemplifies the growing pains of a promising yet young field.
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