Al's story: Turning science into cures

On a spring day in 2007 Albert Raymond was working atop his 18-wheel tractor trailer, securing a stack of pulp logs bound for a paper mill, when he suddenly felt clammy and ashen. His coworkers thought he was having a heart attack.

It turned out to be his first day of a battle with cancer that continues to this day, nearly a decade later.

Al, a self-employed truck driver and grandfather of six from Kingman, Maine, went to his doctor, who detected an abnormally high white blood cell count. The results were a potential early warning sign for chronic lymphocytic leukemia, or CLL, a cancer of the white blood cells.

"When I heard the word cancer I kept saying to myself I hope that's not me, I hope that's not me," Al recalls, shaking his head with downcast eyes.

Because Al had no other symptoms of CLL, such as weight loss or involvement of organs or lymph nodes, his doctor advised a "watchful waiting" strategy. For the next five years he went for regular tests to monitor his blood cell counts.

"Albert was what they called a yo-yo," says his wife, Belinda Raymond. "His numbers would go up and then they would drop right back down."

After five years, tests revealed a spike in his white blood cell count and an enlarged spleen, the organ that filters the blood and plays a role in the immune system.

"Your spleen should be about the size of your fist," says Belinda. "His was the size of a football. So it was making him very sluggish and very tired, and he was losing weight."

Al began receiving chemotherapy at Cancer Care of Maine in Brewer. He soldiered through the usual side effects and even felt well enough to return to work for a few months. Eventually he showed no signs of CLL.

That good news was tempered, however, by another sobering revelation. After he began feeling tired again, a secondary cancer, called myelodysplastic syndromes (MDS), was diagnosed.

MDS is a group of diverse bone marrow disorders with one thing in common: the bone marrow doesn't produce enough healthy blood cells. Ironically Al's MDS was likely caused by one of the chemo drugs he had taken for CLL.

Al was referred to the Dana-Farber Cancer Institute in Boston, where his new oncologist told him that he would need more chemotherapy and a bone marrow stem cell transplant, or else he would succumb to MDS. Fortunately, Al's sister, Estella, tested as a perfect match for donating stem cells.

Al spent a month in the hospital undergoing the procedure in February 2014. He survived the grueling regimen but paid a stiff price for its side effects and complications, including nausea, diarrhea, iron toxicity, dehydration and high blood sugar. In the next months there were more hospital stays, blood transfusions and new medicines.

"His energy and all of his vitality were just like being washed away," recalls Belinda.

Al's immune system, decimated by chemo and then re-seeded by the infusion of stem cells, was highly vulnerable to infection, so he avoided public contact.

"It's scary," he says, "because when they wipe out your immune system, you can catch, at the snap of your finger, I mean anything that's going around. So you've got to be really cautious."

For months he wore a mask and gloves to protect himself from germs. He quit is job and avoided stores and restaurants. He refrained from hugging his four daughters and six grandchildren.

"Anything you consider normal that you would do in a normal day, he does not do unless it's within his home," says Belinda. "You give up your work, you give up your family and your friends. Everything about it is life-altering."

New hope at JAX

Al's cancer odyssey resonates throughout The Jackson Laboratory, where scientists have investigated the genetic origins of cancer for the last eight decades and are developing new and novel approaches to its treatment.

Among the 50 or so scientists working today in JAX's National Cancer Institute-designated Cancer Center is Associate Professor Kevin Mills, Ph.D., who studies DNA damage and repair. Mills' lab is aiming to develop targeted therapies for cancers such as CLL.

"Kevin Mills wants to find a way to attack the cancer without attacking the patient, so that patients like Al can look forward to better treatment options, improved outcomes, and longer, healthier lives," says Edison Liu, M.D., president and CEO of JAX.

Exploiting cancer's weakness

Chronic lymphocytic leukemia is the most common type of leukemia in adults. It affects B-cell lymphocytes, cells of the immune system that originate in the bone marrow, develop in the lymph nodes and normally fight infection by producing antibodies. In CLL, B cells grow uncontrollably and accumulate in the bone marrow and blood, crowding out healthy blood cells.

One of the defining features of CLL, as with many other cancers, is its inability to copy its genome accurately during cell division.

"That is really also the Achilles' heel," Mills says. "The very thing that makes CLL a cancer is also a weakness that we can exploit."

As the genetic copying errors pile up in each successive generation of cells, the accumulation "creates breaks and mutations and nicks all through the genome, all through the chromosomes," Mills explains. "Because of that, cancer cells become critically addicted to DNA repair. They need to have really souped-up DNA-repair mechanisms in order to take care of that damage, in order to survive.

"What my lab has discovered is that if we can take away some of their DNA-repair capacity . . . we can actually cause a CLL cell to essentially mutate itself to death. And so, we have been focused on developing new therapeutic and treatment strategies that leverage and take advantage of this biology."

The importance of DNA repair was underscored recently when three scientists - Tomas Lindahl, Paul Modrich and Aziz Sancar - were jointly awarded the 2015 Nobel Prize in Chemistry for their advances in the field.

"At JAX, we not only understand the mechanism of DNA repair; we are unlocking its potential to serve as the basis of new approaches to cancer treatment," says Liu.

Targeting cancer's over-reliance on DNA repair is a promising alternative to chemotherapy, Mills says. He cites the leukemia drugs Gleevec and Imbruvica as therapies that successfully exploit biological weaknesses of cancer, yielding better results and less-punishing side effects.

"The problem with these drugs - while they're substantially better than chemotherapy - is the cancer cell almost always evolves resistance (to them)," Mills says. "So what we really need is yet another approach in our therapeutic toolbox - drugs that can prevent or forestall the acquisition of therapy resistance.

"If we can succeed, we can develop new therapies that are far more effective, far more long lasting, and have dramatically fewer side effects than chemotherapy," he says.

"Right now, we measure five-year survival rates. But if we can attack tumor evolution at its roots, we can begin to think about 10- or 15- or 25-year survival rates."

Slow road to recovery

Those extended survival rates would be a godsend to cancer patients like Al Raymond, who remains largely confined to his home as he recovers from his disease and its debilitating treatments.

"I think Al's story is a powerful one because it really illustrates the toll that cancer and cancer treatment can take on an individual and can take on a family," Mills says. "Our mission is to improve cancer treatment so that Al's story doesn't have to be realized by future cancer patients.

"There's no reason that a cancer diagnosis should be a devastating diagnosis. And there's no reason that we shouldn't be able to treat cancer in a way that preserves the health of the patient and doesn't leave them with long-term, lingering after effects."

Two years after his stem cell transplant, Al still avoids stores and other public places, fearful that he will catch a germ that could overwhelm his weak immune system.

"I live in a small bubble," he says, but it's "getting a little bit bigger as I progress, as I get better."

Eventually he hopes to go back to his truck-driving job and the freedom of the road someday, if only part time.

"Albert will tell you, he'll say, 'Every day is a good day,' because he is here," says Belinda. "Now we just strive to get to where we actually can get back to what most people take for granted as normal living. We just want to get there from here."

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