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The Mouse That Wouldn't Die: How a Lack of Public Funding Holds Back a Promising Cancer Treatment

Here's the story of a heroic individual bucking the system. But what a system! Pharmaceutical companies spend hundreds of millions of dollars to develop and patent drugs that might prolong cancer patients' lives a few months or years.
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Spring 1999. "Professor Cui, this mouse didn't get cancer. Should I get rid of him?" It was a standard experiment in Zheng Cui's lab at Wake Forest University, North Carolina: Inject inbred mice with cancer cells, not to study cancer, but to produce antibodies for a lipid experiment. "There must have been a mistake," said Cui, "Inject him again." Two weeks later, still no cancer. "Try again with a higher dose!" Still no cancer. No cancer even at a million times the lethal dose. Cui decided to breed the mutant mouse.

My husband, Tom Haines, and Chinese-born Zheng Cui are long-time colleagues in lipid research. When we visited his lab in 2001, Cui showed us stacks of cages holding hundreds of little brown cancer-resistant mice. He had already worked out the genetics of the mice, and bred the resistance trait into a second variety of lab mice. He had also discovered that while young mice don't get cancer at all when injected, older mice get cancer which then spontaneously disappears! The mechanism remained a mystery.

In fall 2002, my husband introduced Cui to leading cancer researcher Lloyd J. Old, director of the Ludwig Institute for Cancer Research at the Memorial Sloan-Kettering Cancer Center and founder of the New York Cancer Research Institute. Old was enthusiastic. As a member of the National Academy of Sciences, Old submitted Cui's article on spontaneous regression of advanced cancer in mice to the prestigious Proceedings of the National Academy of Sciences (PNAS), where it appeared in March 2003. Cui also published a personal account of his discovery.

With support from Old's Cancer Research Institute, Cui continued experiments on the mice. He injected white blood cells from cancer-resistant mice into non-resistant mice with tumors. Amazing! The tumors shrank and disappeared. More experiments revealed what was killing the tumors: granulocytes, the largest class of white blood cells. Granulocytes look speckled under a microscope because they're packed with little torpedo-shaped particles. They home in on invading bacteria and inject the torpedoes, which then blow holes in the bacterial membrane. It appeared that granulocytes were doing the same to cancer cells. The cancer-resistant mice showed that some individuals have super-aggressive granulocytes. With Old as a coauthor, Cui's second PNAS article, on transferable anticancer immunity appeared in March 2006.

Cui could then have settled into a successful career studying cancer-resistant mice. Instead, he took an audacious step: If some mice have super-resistance to cancer, he proposed, perhaps some humans do too.In fact, perhaps transfusions of granulocytes from super-resistant humans could treat cancer patients! Preliminary lab tests on human granulocytes indicated some people are indeed super-resistant.

Cui began to seek funding to test the transfusion theory. He already knew support wouldn't come easily; blood transfusions are old technology and so can't be patented. The pharmaceutical industry of course would take no interest. And as Cui found, clinical oncologists resist anything outside the usual treatments, even when they have nothing more to offer their patients. Finally, in 2008, he obtained a grant and FDA approval for a clinical trial at Wake Forest. But shortly before the trial was to start, the university cancelled it without explanation.

Nothing daunted, Cui raised money from private donors and got FDA approval for a clinical trial at the South Florida Bone Marrow/Stem Cell Institute, starting in 2009. The patients must all have terminal metastatic cancer, with no further treatment options. The trial costs average over $140,000 per patient. Granulocyte donors are healthy young students from nearby Florida Atlantic University. The study must follow an elaborate FDA protocol and must include 29 participants before any long-term evaluation can be released. Cui also set up a trial at a location in China.

When we spoke to Cui over a year ago, he had good news and bad news. The good news: The Florida patients had had a very encouraging short-term response to the treatment; the transfused granulocytes effectively killed cancer cells. The bad news: His wife was diagnosed with stage IV squamous cell carcinoma with massive metastases to all her major organs (lungs, liver, spleen and kidneys) and was given months to live. She had run out of conventional treatment options after partial surgery and chemotherapy. But he planned to take her to China for treatment at his other trial site in March 2013.

Two months ago, good news and bad news again. Good news: we met with Cui and his wife. She looked terrific. To the astonishment of her doctors, her condition appears completely stable after 14 months, with no further treatment of any sort. She told us the transfusions gave her a high fever, but no other side effects. Bad news: In Florida, the institute has so far recruited only 20 of the 29 participants required to complete the trial. With Lloyd Old's death in 2011, private funding is drying up. At Wake Forest, due to cutbacks in NIH funding and other problems, the university faces severe financial difficulties; Cui's research lab is down to one assistant. And in China, the trial has become stuck in a bureaucratic bog. Cui still isn't giving up.

So here's the story of a heroic individual bucking the system. But what a system! Pharmaceutical companies spend hundreds of millions of dollars to develop and patent drugs that might prolong cancer patients' lives a few months or years. Clinical oncologists make a good living treating patients with these drugs; they regard alternatives with extreme skepticism. How then can a promising unorthodox treatment get a decent trial? At the least, Zheng Cui has given us a poster mouse for public funding of basic scientific and medical research.

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