A few months back, I found myself engrossed in a TV show alongside my husband and in-laws, which highlighted a particularly insidious parasite found in raw fish, known for causing excruciating pain in humans and other animals. Usually this is taken from eating raw fish such as sashimi or sushi which are delicacies here in Japan. The show featured interviews with some famous people here in Japan and one of them was Naomi Watanabe(famous entertainer) who had suffered from this parasite. The symptoms described were severe, with suffering from intense vomiting and abdominal pain, likened to feeling near death.

Interestingly, this formidable creature, which I might daringly refer to as a 'little monster', has shown potential in the medical field, particularly in cancer treatment. Professor Shinji Sakai from Osaka University has been at the forefront of this intriguing research. His work suggests that the Anisakis parasite could be instrumental not only in detecting cancer but also in treating it. This groundbreaking research, published two years ago in the Research at Osaka University offers a glimmer of hope in the fight against cancer, transforming a once-feared parasite into a potential ally in medical science. I felt it was important to share more about this remarkable development and the ongoing research that could revolutionize cancer treatment.

Upon first encountering Professor Sakai's article, I was filled with optimism about the future of cancer treatments and their life-saving potential. My motivation for delving into this topic is deeply personal, not just driven by curiosity. My mother is a cancer survivor, and the memory of the fear and uncertainty we faced upon her diagnosis remains vivid. I want to clarify that I am not a medical expert. The following article, translated from Japanese to English, is based on information from the original publication, which is cited at the reference section below.

Why Anisakis as a research subject?

Professor Sakai's inspiration stemmed from the work of HIROTSU Bioscience, a venture company developing 'N-NOSE', a test that employs nematodes for early-stage cancer risk diagnosis. He became intrigued after reading an article from HIROTSU Bioscience, which detailed the genesis of their research. It originated from a medical report describing a patient with Anisakis food poisoning. During the attempt to remove Anisakis from the patient's stomach, doctors noticed the parasites congregating and attaching themselves to areas affected by stomach cancer. This observation sparked the idea of using nematodes for cancer diagnosis.

Additionally, Professor Sakai's personal history played a role in his interest. His childhood was marked by frequent fishing trips with his father, who was an avid fisherman. They often caught mackerel, a species commonly infested with Anisakis. He recalls his father's caution about consuming mackerel quickly to avoid stomach aches. This early exposure to Anisakis left a lasting impression on Professor Sakai, making the parasite a familiar subject in his life.

Why hasn't Anisakis been widely used in past research, and what have you discovered since starting your study?

The main challenge is mass production. While it's relatively easy to grow and multiply species like sea elegans, Anisakis hasn't been successfully bred or mass-produced in controlled environments. This means we rely on naturally occurring specimens, which makes them less suitable for consistent research material.

How did you develop the innovative idea of coating Anisakis with a film?

The concept originated from my regenerative medicine research, where I had developed a technology to coat the surface of animal cells with a membrane. When exploring the use of Anisakis in cancer treatment, we faced the question: "How can we add a therapeutic substance to Anisakis for treatment purposes?" Applying a thin film, a technique I had previously used, seemed like a viable solution. This approach allows us to incorporate the therapeutic substance into the film, effectively equipping the Anisakis with a functional 'suit' while maintaining their viability.

Additionally, the coating itself was surprisingly easy to apply. The main concern was about whether the film would break if the Anisakis moved around after coating, but in the end it didn't break and it took root well. Image below shows: Anisakis untreated in the grey image and the green one is coated with fluorescent gel thin film.

What is the specific process used to apply the coating?

The method we use is using an enzyme called peroxidase, which is extracted from horseradish. When peroxidase is immobilized on the surface of Anisakis, the enzyme acts to connect the molecules, and a reaction occurs only on the surface, forming a membrane. A molecule that functions like an anchor penetrates the cell membrane. This molecule is attached to an enzyme and then brought into contact with the Anisakis surface to secure it in place. This technique, initially developed for coating animal cells with membranes, involves fixing the molecule first. Then, it's used as a base to weave other molecules together, forming a membrane. Essentially, it's like stitching a membrane onto the surface of the Anisakis.

What challenges must be addressed for Anisakis to be effectively used in future cancer treatments?

The primary concern is that Anisakis is a parasite toxic to humans, so allowing it to remain in the body indefinitely poses a significant risk. Therefore, it's crucial to develop measures for its removal after it has served its purpose. One potential solution is to incorporate a mechanism into the 'suit' that would eliminate the Anisakis once its role is complete. Another significant challenge is mass production. For Anisakis to be viable in practical treatments, we need to consistently produce a homogeneous product. However, this is a major hurdle, as the technology for breeding Anisakis in a controlled environment is not yet established.

Fun curiosity about how bluefin tuna kills this parasite?

Anisakis can infect tuna just like it can other fish species. In a unique scenario, if an Anisakis larva infests an Atlantic bluefin tuna, it might mistakenly believe it has found a warm-blooded host. This is due to the tuna's ability to raise its body temperature. Mistakenly, the parasite begins its transition from the third-stage larva (L3) to the fourth stage (L4), but ultimately fails to survive because the tuna's temperature is not stable, leading to the parasite's demise.

The Anisakis worm's choice of location within its host varies depending on the host species. It may encapsulate itself in various organs such as the liver, intestines, gonads, or the abdominal cavity's wall. This preference also varies depending on the Anisakis species.

Reference:

Laboratory: http://www.cheng.es.osaka-u.ac.jp/sakailabo/home.html

The Sankei Shinbun

Osaka University

Research at Osaka University

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