Sometimes discoveries are made when you are looking for something else. I was searching through scientific journals for some history of chemotherapy and rosy periwinkle, when my husband Ben’s grandfather – James D. Havens – popped up. Ben never met his grandfather, but our walls are covered with his artwork — intricate colorful woodcuts and watercolors. James Havens was both an artist and the first American treated with insulin in the U.S. I knew this, but hadn’t expected to find a connection while reading up on plants and chemotherapy.
Stories of discovery are also seldom a straight shot. In in this case, the history of vincristine and vinblastine, some of the first effective anticancer drugs isolated from a plant began with diabetes. Robert Noble, credited with the discovery, was looking for an oral alternative to injectable insulin. When taken orally the hormone is digested, and becomes ineffective. The Madagascar (rosy) periwinkle – a plant reminiscent of the purple periwinkle many of us use for groundcover – was one candidate. At the time he was working with James Collip, the scientist who decades earlier, isolated the insulin that saved James Havens’ life.
James was around 15 when his pancreas stopped making the hormone that enables cells to use sugar for fuel. When cells starve for lack of sugar, the body begins burning fat. Burning fat produces ketones, if a body produces large amounts, the blood can become dangerously acidic. So not only did his body begin to consume itself, but the high levels of ketones had him on the verge of lapsing into a coma. In the early 1900s when Jim was diagnosed, the only treatment was essentially controlled starvation. Five years later, subsisting on a diet of 200 calories a day, the 5’8” twenty-year-old weighed in at 85 pounds. By May of 1920 his father wrote to a friend that Jim had become a mere shadow.
Just to the north of James’ home town of Rochester, N.Y. scientists in Toronto, Canada, were working on a cure for diabetics. They discovered that pancreatic secretions collected from animals, could stave off diabetes in other animals. But the secretions were essentially a soup of hormones and proteins and other chemicals – too crude a mixture to risk injecting into humans without serious side effects. Collip, a biochemist, figured out how to make a cleaner, safer preparation. In January of 1922, the group treated fourteen year old Leonard Thompson, all sixty-five pounds of him. Four months later, a few doses were shipped to Rochester. Jim received his first injection on May 22. There were setbacks and risks. The dose had to be increased. There was the potential for an allergic reaction; or infections at the site of injection. At one point, the injections had become so painful that his doctor withheld the needle for a few days, fearing for Jim’s life. Those working in the field seemed to agree than an oral drug would be an improvement, and plant extracts were one possibility.
After these initial discoveries and before the war Robert Noble, a few years out of medical school, began working with James Collip. During the war they spent some time figuring out how best to traumatize laboratory animals (presumably to aid traumatized soldiers) – by spinning them around in a drum. After the war they refocused on curing disease.
In 1952, Noble’s older brother, a physician with an interest in diabetes received in the mail a packet of rosy periwinkle leaves. They were sent by another physician working in Jamaica with ties to Toronto, Dr. Johnson. Locals there claimed that tea made with periwinkle leaves relieved the symptoms of diabetes and Johnson was curious. The older Noble passed the packet on to Collip’s laboratory — perhaps they could find some active ingredient in those leaves. The lab, according to the younger Noble, had already been tinkering with plant extracts following up on various folkloric connections.
When an extract of the leaves failed to calm the sugary blood of diabetic rats and rabbits, Noble and his colleagues tried an injection. That didn’t work either, but there was a curious side-effect. Rats exposed to large amounts of periwinkle extract died of infection[i]. Something in the plant’s leaves suppressed the immune response, and in particular, depressed the white blood cell count. It was this observation, Noble later wrote, that eventually led to the anti-cancer drugs (in particular antileukemic drugs). At the time, drugs isolated from plants had been in use for nearly a century (plants and plant extracts have been used since forever) – morphine and quinine to name a couple. This would be the first for cancer where the need was so critical.
James lived until 1960. In the years since his initial treatment, an oral treatment for diabetes yet to emerge although some plants and herbs are used to moderate the symptoms. In 1963 his grandson Ben was born and his family eventually became mine too. James Havens’ prints and water colors hang on our walls and in museums around the country: ripening blackberries in deep purples, reds and green; a butter yellow sunflower standing against the blue sky; soft lily petals stretching across the page; stars that swirl into the night sky. Plants may have failed to provide a better cure, but they fueled his artist’s soul.
If you are interested in more about insulin: The Discovery of Insulin, by Michael Bliss
And the Readers Digest version of James’ story is here