Dainty flower is relentless cancer killer in disguise

Photo cour­tesy of Car­olyn Lee-​​Parsons.

When I was in high school I read a book called Tales of a Shaman’s Appren­tice that I thought was going to define the rest of my life (I’ve always been kind of dra­matic like that). It was about dis­cov­ering the chem­ical com­pounds found in plants that cul­tures have been using for cen­turies, even mil­lennia, to treat dis­ease. I was con­vinced I’d found my calling: I would hike through rain­forests with indige­nous med­ical experts col­lecting del­i­cate spec­i­mens to bring back to the lab and study. Actu­ally, a not-​​so-​​small part of me still thinks this sounds pretty much amazing.

The book and the dream came flooding back to me recently when I met chem­ical engi­neering pro­fessor Car­olyn Lee-​​Parsons, Northeastern’s res­i­dent expert on the Mada­gascar Peri­winkle. This dainty little flower may look like your average garden plant, but lurking behind an unas­suming dis­guise of pink petals and pretty leaves lies an impor­tant phar­ma­ceu­tical pro­duc­tion facility that has been sup­plying the people of Mada­gascar and much of the tropics with treat­ments for var­ious dis­eases for centuries.

In the mid-​​twentieth cen­tury, two of the com­pounds pro­duced in its sap were iden­ti­fied as superb anti-​​cancer drugs. Vin­blas­tine and vin­cristine are alka­loids, or basic com­pounds, that halt the pro­duc­tion of tubulin, which is like the skeleton of a cell. “It’s really like a chem­ical arsenal that they unleash to kill bac­teria, fungus, insects,” explained Lee-​​Parsons. The only problem with the busi­ness plan that exploits this native arsenal, is that the prod­ucts are extremely expensive.

The com­mer­cial drug that con­tains nat­u­rally har­vested vin­blas­tine costs $2 mil­lion per kilo­gram, while the one con­taining vin­cristine costs $15 mil­lion per kilo­gram. Each drug-​​producing cell in the peri­winkle plant con­tains but a tiny frac­tion of the anti-​​cancer drug: 0.0005 per­cent of the cell’s dry weight. It’s also very dif­fi­cult to con­trol the pro­duc­tion of the plants: things like sun­light, infec­tious bac­teria and sea­son­ality make farming a less than ideal model for phar­ma­ceu­tical drug production.

But Lee-​​Parsons is taking advan­tage of an inter­esting quirk of life to increase the per­centage of drug pro­duced by the plant cells. Just like the human body, where dif­ferent organs have dif­ferent spe­cial­ties and thus pro­duce dif­ferent cell-​​types, the leaves, roots and shoots of the Mada­gascar Peri­winkle each has its own par­tic­ular job within the organism. “By under­standing the plant biology,” she explained, “we can take any part of the plant and by applying spe­cial plant hor­mones we can direct its development.”

Photo by Just Chaos via Flickr.

Her team grows little flasks full of leaves or roots or even just cell suspensions–which she said look some­thing like green apple­sauce. In the wild, of course, none of these would sur­vive since they all rely on each other. The leaves do pho­to­syn­thesis to secure oxygen for the whole system. The roots suck up nutri­ents and water from the ground. Without leaves, and thus without oxygen, the roots are pretty des­ti­tute. In the lab, where Lee-​​Parsons’ team is like a band of busy nurses, all working to keep these starving foundlings alive. They pro­vide spe­cial growth media that allow the var­ious cell-​​cultures to thrive, even in the absence of their com­pa­triot plant parts.

Now that the cells are being expertly cared for, they no longer have to worry about keeping them­selves alive. Now, when Lee-​​Parsons applies cer­tain hor­mones to spark the pro­duc­tion of drug-​​producing cells, they can actu­ally devote some resources to that job.

I’m not a big gar­dener. I tend to forget that basic things like water and sun are required to keep my house­plants alive, so when they start dying I wonder why (an early cue that my career as a shaman’s appren­tice was unlikely). But my fiance is and he recently edu­cated me on the fact that if you cut off the flower heads of herb plants, they will be able to devote more resources to making leaves. They would really rather repro­duce so after a while they start sending out seed-​​containing flowers but we, wanting tasty salad dress­ings and such, nip that process in the bud. Lit­er­ally. This is sim­ilar to what Lee-​​Parsons is doing in the lab. She allows the plant cells to focus on a single job — drug pro­duc­tion — without having to worry about all the other things that go into sur­vival in the stan­dard environment.

By com­bining the knowl­edge of var­ious types of experts, from biol­o­gists to ana­lyt­ical chemists to geneti­cists, Lee-​​Parsons engi­neers sys­tems that can pro­duce phar­ma­ceu­tical prod­ucts in much greater abun­dance than the plants nat­u­rally do on their own. If she can bring the con­cen­tra­tion up by even a frac­tion of a per­cent, she could help to sig­nif­i­cantly reduce the cost of the drugs.