The Story of Folic & Anti-Folic acid


Today's Google Doodle celebrates the birth anniversary of scientist Lucy Wills who discovered Folic acid. The discovery has an India connection - the candidates for her research were mill workers in Bombay. I remembered reading about her in the very excellent book "The Emperor of All Maladies" by oncologist Siddhartha Mukherjee.

That book had also helped me know about India's science hero, Yellapragada Subbarao—or Yella. Hope Google commemorates his birthday too on 12th January
Aminopterin, a brainchild of SubbaRow....reverses the vitamin action of folic acid and is called an anti-folic or folic acid antagonist. It provided for the first time some semblance of treatment for leukaemias. It initiated the chemotherapeutic approach to treat widespread cancers or cancers not amenable to surgery. Methotrexate, the modified aminopterin, has singly improved the survival of young women suffering from choriocarcinoma, the cancer of the after-birth mimicking pregnancy.

Excerpt from "The Emperor of All Maladies" on the story of folic & anti-folic acid -

In 1928, a young English physician named Lucy Wills, freshly out of the London School of Medicine for Women, traveled on a grant to Bombay to study this anemia. Wills was an exotic among hematologists, an adventurous woman driven by a powerful curiosity about blood willing to travel to a faraway country to solve a mysterious anemia on a whim. 

Eight thousand miles away, in the cloth mills of Bombay (owned by English traders and managed by their cutthroat local middlemen), wages had been driven to such low levels that the mill workers lived in abject poverty, malnourished and without medical care. When English physicians tested these mill workers in the 1920s to study the effects of this chronic malnutrition, they discovered that many of them, particularly women after childbirth, were severely anemic. (This was yet another colonial fascination: to create the conditions of misery in a population, then subject it to social or medical experimentation.)

...unlike Minot’s pernicious anemia, she found that the anemia in Bombay couldn’t be reversed by Minot’s concoctions or by vitamin B12. Astonishingly, she found she could cure it with Marmite, the dark, yeasty spread then popular among health fanatics in England and Australia. Wills could not determine the key chemical nutrient of Marmite. She called it the Wills factor. Wills factor turned out to be folic acid, or folate, a vitamin-like substance found in fruits and vegetables (and amply in Marmite). 

When cells divide, they need to make copies of DNA—the chemical that carries all the genetic information in a cell. Folic acid is a crucial building block for DNA and is thus vital for cell division. Since blood cells are produced by arguably the most fearsome rate of cell division in the human body—more than 300 billion cells a day—the genesis of blood is particularly dependent on folic acid. In its absence (in men and women starved of vegetables, as in Bombay) the production of new blood cells in the bone marrow halts. Millions of half-matured cells spew out, piling up like half-finished goods bottlenecked in an assembly line. The bone marrow becomes a  dysfunctional mill, a malnourished biological factory oddly reminiscent of the cloth factories of Bombay

Enzymes and receptors in cells typically work by recognizing molecules using their chemical structure. But a “decoy” molecular structure—one that nearly mimics the natural molecule—can bind to the receptor or enzyme and block its action, like a false key jamming a lock. Some of Yella’s molecular mimics could thus behave like antagonists to folic acid.

Comments