That effort has taken another four years. In January, Svanborg released the team’s most recent findings, bolstered by the work of new collaborators, including researchers from the renowned Karolinska Institute in Stockholm and Oxford University in England. The studies explain how transformed alpha-lac snuffs out cancer and other risky cells, and characterizes the protein down to the molecular level. And they announced that not only does it kill cells, it eliminates pneumococcus bacteria, too. Svanborg, with her long-standing interest in infectious disease, is as excited about this finding as any. She envisions using alpha-lac as a tonic to stop infections before they begin.
Breast-fed infants take in more than just nutrition with their mothers’ milk. The American Academy of Pediatrics calls breast-feeding “the ideal method of feeding and nurturing infants.” Like a magic elixir, the milk promotes the nursing infant’s general health, growth, and development, while significantly decreasing the risk of infection. Breast-feeding has also been related to possible enhancement of cognitive development. It protects the nursing infant against a slew of diseases, including diarrhea, lower respiratory infection, otitis media, bacteremia, bacterial meningitis, botulism, urinary-tract infection, necrotizing enterocolitis, sudden infant death syndrome, insulin-dependent diabetes mellitus, Crohn’s disease, ulcerative colitis, and allergic diseases. And, of course, there is evidence that mothers’ milk protects against lymphoma and carcinomas.
The team has given the new protein a name: HAMLET for Human Alpha-lactalbumin Made LEthal to Tumor cells (appropriate for a Scandinavian hero that alters its nature to take lethal action). They now know just how the protein changes into a cancer assassin. One key is the acid content of its surroundings. When Svanborg initially prepared milk to pour over cells, she added acid to the solution, hoping to separate out the microbe blockers. Little did she know that this acid bath, like some magic potion, would transform the well-mannered alpha-lac into HAMLET. But acid alone wasn’t enough. Another mysterious factor was needed. That, too, turned out to be a component of the milk itself. (The lab has not yet made its identity public).
Imagine a mother nursing her baby. Her milk contains alpha-lac in its ordinary, lactose-producing form. It also contains lots of the secret component. Milk cascades into the child’s digestive tract, where it encounters an environment radically different from the mammary gland in which it was produced. The infant’s stomach is awash in powerful digestive acids. In fact, it almost exactly mimics the acid level of the milk solution that changed the alpha-lac to its cancer-killing form in Svanborg and Håkansson’s experiments. The acid content in the child’s gut probably implements the crucial shape shift, transforming alpha-lac into HAMLET.
Now that the team can generate genetically engineered HAMLET, they can make changes in it, helping them learn the function of its structural parts. “That means we know what we’re doing,” Svanborg says. “I think people will start seeing this as a fact.”
“My prediction,” agrees Stevens, “is that with the current publications, interest in this research will increase. People will see this as real and novel and important.”
As they await reaction from the scientific community, the team is exploring how to turn HAMLET into a usable treatment for cancer and bacterial infections. And that becomes the topic of the team during dinner at Svanborg’s home on a wet January night. “We often work here,” says Svanborg. “We use the house as an extension of the lab.” A snug cottage with white plaster walls and wide wood-plank floors, a brisk walk from the cathedral, it fills with people, the windows fogging.
Anders Håkansson and graduate student Malin Svensson working late as usual.
The team has come directly from the lab, as long hours are the norm these days. Anders Håkansson is here, along with graduate student Malin Svensson, technician Ann-Kristin Mossberg, chemist Sara Linse, and a new colleague, physician and immunologist Hans Belfrage. They crowd around Svanborg’s dinner table for halibut casserole, bread, and red wine, with blue cheese tart and grapes for dessert. (“Catharina has had this table for a long time,” says the effervescent Svensson, who tracked down the secret ingredient in HAMLET. “Students have been sitting here writing papers with her for years. If only this table could talk. . . .”)
“HAMLET looks so good and so exciting,” says Belfrage, nursing his coffee. “But we need to consider the pros and cons.” Tall and grave, Belfrage resembles a young Max von Sydow striding through the bleak landscape of early Bergman movies. Svanborg has entrusted him with the responsibility of escorting the discovery into the clinic for trials.
The first step is to test HAMLET as a tumor killer in animals. Svanborg and her team hope that because HAMLET is a naturally occurring substance, it might not be toxic like so many other cancer drugs. They’ve already tried it in mice, who tolerate very high doses with no side effects.
If animal tests go well, the next trials will be with humans, a process that involves three stages—one for safety, the next to see if the protein kills cancer in a limited number of people, and the last to turn it loose in a large group. That can take years. And then, says Svanborg, “A major pharmaceutical company must become convinced that this is worth their investment. But if we can demonstrate that HAMLET works, I think no major company would be able to refuse.”
“This is a substance that kills lots of tumor cells, every cancer we test it against,” Svensson says. “Lung cancer, throat cancer, kidney cancer, colon cancer, bladder cancer, lymphoma, leukemia, and pneumococcus bacteria too.”
“That’s a very big pro,” says Belfrage.
“But cancer cells in the lab don’t necessarily indicate the response of human tumors,” Håkansson reminds the group.
“That may be a con,” Belfrage agrees. “The only way to know is to test in people. It may be possible to do a small-scale, pilot safety study quite soon, perhaps in six months. We don’t want to wait years.”
Svanborg smiles at the group crowded around her table. This is the life she enjoys—working to further her colleagues as they prepare to lift another veil from the mysteries and magic of HAMLET. “When we started doing research here, in this little town, in this little country on the edge of the known world, few people were aware of it. Now that this enormous opportunity has come to us, we want the world to know.”