It's been five years since George Miller watched a friend die of ALS. Now, he says, it's his turn.
"What is...is," George says, his speech strained and distorted by the muscle degeneration inherent in amyotrophic lateral sclerosis (ALS), a disease that few survive beyond five years. "I remember my friend, Shawn, saying that he felt sorry for himself for 10 minutes a day. I don't even do that. I figure that the more time I spend worrying about what I can't do, the less time I have to do the things I can."
Like his father, George was born in the rural Maine farmhouse that he and his wife, Janice Von Brook, now call home. It is far away, both literally and figuratively, from the high tech environs of The Jackson Laboratory, where Janice and her daughter, Carol Lamb, have worked as senior administrative assistants for many years. Despite the distance - Janice and Carol commute more than an hour each way - there is a close bond with the Laboratory. When the family helped to organize the first ALS Walk in Bangor in August 2008, many employees, including ALS researcher Gregory A. Cox, Ph.D., and his research team, were among the first to sign up.
The farmhouse is the showpiece of the Katahdin View Farm near Bangor. Although the 100-acre farm in Hampden is 70-something miles from Maine's highest mountain, you can see Katahdin from a hilltop on the windswept acres where the couple raises pigs, chickens and registered Charolais cattle. A cranny in the farmhouse mudroom is crammed with well-worn coveralls, muddy chore boots and an array of livestock trophies, including those George collected last summer for showing the best bull and cow at Maine's iconic Blue Hill Fair.
As they've been for nearly all of his 66 years, George's animals are his life. His barnyard beasts anchor a 24/7 existence devoted to farm chores and animal husbandry challenges that, he says with a smile, never fail to present themselves in bad weather during the dark of night. While George's ALS symptoms now affect his balance, they haven't stopped him. Not yet, anyway. His movements are measured, but he doesn't spill even a kernel as he scales a maze of pig panels to feed his sows from buckets of corn and other grains.
"His attitude has been absolutely wonderful," Janice says. "I remember early on, telling him how sorry I was he has to go through all this. And what he said surprised me: 'Somebody has to do it.'"
George's ALS symptoms surfaced as slurred speech, which Janice first noticed when George spoke at a meeting in February 2005. On the drive home, George admitted he had known something was wrong since December. A neurologist in Boston confirmed that George either had ALS or some close cousin of the always fatal disease, a progression of motor neuron failures that leaves its victims' minds intact as it gradually robs them of control over muscle movement. What began with George as trouble speaking has since progressed to trouble swallowing and breathing.
There's no apparent genetic link between George and his condition. There's no family history of ALS, which isn't unusual. ALS researchers such as Dr. Cox at The Jackson Laboratory and those elsewhere have found that fewer than 10 percent of the 5,600 new ALS cases diagnosed in the United States each year can be directly attributed to family genetics. With at least 90 percent of ALS cases being random, this disease can potentially surface in anyone. ALS experts are the first to admit that there are many more questions than answers.
"This disorder is so devastating, and our knowledge base is still so incomplete," says Dr. Cox, an associate professor, whose Jackson Laboratory research team has been studying the genetic elements of a wide range of motor neuron diseases for the last nine years. "And, in terms of the sporadic cases, we're all still scratching our heads. We really don't know what triggers these cases. We're just hopeful that what we can figure out in the handful of genetic cases might apply to sporadic cases, but that's a big 'might.' We have no idea if it will or not, but it's the only handle we have.
"Our expectation is that there will be a genetic susceptibility to ALS, that it's not completely random. All of the data suggest that it is not transmissible, so it's not something you can ‘catch.' Right now it looks relatively random, in terms of who is susceptible and who is not. Our hope is that, once we have the data, there will be underlying patterns of genetic susceptibility and then environmental triggers might be identified."
The mouse models for ALS created at The Jackson Laboratory are widely used in ongoing motor neuron disease research worldwide. They were engineered to include multiple copies of a mutated gene associated with some inherited ALS cases. With insights gleaned through in-house research and at other labs, new ALS models are continuously under development.
"Our ALS models remain the best tools we have," says Kevin Seburn, a research scientist working with Dr. Cox. "We know we're limited by how little we know. If we understood more, we would make a better model, but we don't. We're at this stage in the field where it's really hard to know what is the best model for those 90 percent of ALS cases for which we have absolutely no understanding. The problem is that we just don't know enough. At least not yet."
The Jackson Laboratory's insights into ALS are being enhanced through in-house collaborations with Jackson scientists who are investigating other neurodegenerative diseases, including Parkinson's and Alzheimer's. Dr. Cox points out, too, that the motor neuron degeneration inherent in ALS mimics the normal processes of aging, but at a highly accelerated pace.
"The aging research under way here is potentially ALS-related," he says. "Motor neuron death is a part of aging. But in ALS it's accelerated. When you age, you lose a motor neuron here and there, but you have hundreds and hundreds within a muscle, so if you lose one, it's not that big a deal. You lose another one next year, still no big deal. But, with ALS, when you lose 50 at a time, and they all start dropping out, that's a very big deal."
The Jackson Laboratory is unique in its commitment to improving existing mouse models for ALS research and developing new models, Dr. Cox says.
"Beyond this campus, there are very few mouse geneticists working on ALS," he says. "We have clinicians, we have pharmaceutical companies, and we have people doing imaging. We have people coming into this from completely different areas, and they may not have had much experience with working with mice.
"At The Jackson Laboratory, we're in a position where we can share our expertise with ALS mouse models and, by doing so, improve the quality of pre-clinical trials. What's likely is that it will be Jackson mouse models that will make ALS therapies happen. We've already made them better and, as new genetic mechanisms are better understood, we can improve on that some more."
George Miller is part of the effort to improve therapies. Approximately 160 walkers participated in the ALS walk. The walkers, including George and the 30-member "Fighting for Farmer George" team, raised more than $32,000 in support of more, and better, ALS research.