On the fifth floor of the Fred Hutchinson Cancer Research Center in Seattle, Dr. Jim Olson and his team are training a robot to process and purify hardy peptides known as knottins, some of which are natural compounds made by plants and animals as diverse as sunflowers and scorpions.
The robot will be capable of churning out work at 50 times the speed of Olson’s best scientists. Olson, a neuro-oncologist at Seattle Children’s Hospital, walks fast, talks fast and carries a big ambition because of the young cancer patients he has known. He once lost an 11-year-old patient named Violet to brain cancer. That experience inspired him to create Project Violet, which raises money for his laboratory’s work at Fred Hutch.
Olson believes knottins can be engineered into therapies that may help thousands of patients to avoid Violet’s fate. He aims to use them not just for brain cancer, but also for Alzheimer’s and other neurodegenerative diseases and maybe even arthritis.
The reason he sees such a big therapeutic landscape for these compounds has to do with their folded and knotted shape — hence the coinage “knottins.” Their knotted shapes allow them to go places in the human body where other drug therapies can’t easily reach. Olson proudly wears on his upper arm a simplified tattoo shaped liked one of his favorite knottins.
Olson is probably best-known for having invented Tumor Paint, a product that uses the capability of scorpion venom to cross the blood-brain barrier and bind to cancerous tissue. As noted in the September 2012 issue of Seattle Business, he hitched that protein to what he calls a molecular flashlight, a dye that fluoresces when exposed to near-infrared light.
The clinical version of this paint, BLZ-100 Tumor Paint, won designation from the Food and Drug Administration in 2014 for use on brain tumors. When injected into a patient, the engineered molecule travels to the tumor and makes it glow so surgeons can see its precise boundaries. BLZ-100 is slowly working its way through clinical trials and is being developed by Blaze Bioscience, a private company cofounded by Olson. Recently, Blaze published in the medical journal JAMA a report about research on mice that shows BLZ-100 may eventually be helpful for treating head and neck cancers.
While working on Tumor Paint, Olson became convinced his team could engineer other knottins for human therapies. Different knottins travel to different parts of the body. Some can cross the blood-brain barrier, making them potentially useful for delivering drugs to the brain, but others have distinct characteristics that allow them to avoid being destroyed by stomach acid and human enzymes. One he has studied in mice travels to the joints, and he imagines hitching a pain reliever to it as an improvement on oral medications for arthritis.
Pharmaceutical companies have known about knottins for years. For a variety of reasons — including the inability to grow them easily in yeast or bacteria, the typical laboratory workhorses — they have been unable to tap their power. Olson discovered he could replicate the proteins by “growing” them inside human kidney cells, a crucial breakthrough. Olson’s team changes the proteins, in some cases giving them payloads to kill cancer cells. Once engineered, they are called optides — an optimized peptide.
Olson’s lab at Fred Hutch has a staff of about 30. He declined to say specifically how much money it spends in a year but described it as similar to a biotech company that might spend $5 million in a year’s time. It occupies about 40,000 square feet.
The laboratory robot, which cost about $750,000, was custom designed to enable Olson’s lab to generate, process and purify more knottins. An expert scientist might be able to process 10 molecules per week. The robot can produce 500 in the same time.
The idea for the robot came as Olson was talking about his work with a software executive. “He asked me: ‘What is your pain point?’” Olson remembers. Olson, who loves borrowing strategies from software engineering or the tech sciences and applying them to medical research, says automating the process of growing and purifying new compounds struck him as a “pain point” he could target.
That “aha” moment occurred two years ago; the robot arrived earlier this year. By the end of the year, the lab hopes to have a library of 10,000 optides, which will give scientists a far better chance of finding one likely to attach itself to a target of interest, such as a particular lung cancer cell.
Department of Arts and Sciences
Jim Olson likes his team to draw inspiration from art and music. He invited his team to try glassblowing at the Museum of Glass in Tacoma, and their product — some lavender teardrop shapes — hang in the laboratory window in honor of Project Violet.
Two years ago, Olson decided to produce a folk-pop CD — The Violet Sessions — featuring local artists Hey Marseilles, Noah Gundersen, Ben Fisher, Le Wrens, OK Sweetheart, Naomi Wachira and St. Paul De Vence. The crowdfunded project helped raise more than $10,000 for the Olson lab’s research. The CD is still available online and the music can be downloaded via iTunes.
“Creativity is dulled by meetings and piqued by novel experiences,” Olson observes. This appreciation of creativity has been particularly helpful in generating fundraising ideas that are crucial to the success of his laboratory. For example, lab employees came up with the idea of carnival games to help attendees at a recent fundraiser understand the fundamental science taking place. They created an optide bean bag toss with bags of different sizes representing a range of drug candidates. These “drug candidates” had to be tossed into containers of varying sizes that represented the drug targets, such as assorted cancer cells. The event raised more than $500,000.