Outside the lab

Five years after being diagnosed with Stage III lung cancer, Ellen Smith, 63, of Centennial, is newly married and traveling the world again.

Durango third-grader Annelise Heinicke, who has cystic fibrosis, is looking forward to a long, healthy life.

Haxtun farmer Dan Anderson has seen his wheat seed business thrive, thanks to researchers who have helped boost the yields of wheat and reduce its susceptibility to disease and drought.

Jessica Sabo, a 26-year-old graduate student who lives in Boulder, is able to confidently speak her mind after a lifetime of paralyzing stuttering.

“I feel so fortunate to have ended up in a place where so much research on stuttering has been done,” said Sabo, whose therapist at the University of Colorado Boulder is renowned in the field.

Smith, Heinicke, Anderson and Sabo are among thousands of Coloradans who benefit each year, on a deeply personal level, from living in a state rich with academic research across the sciences. The economic impact on the state alone is noteworthy:

• CU’s four campuses — CU-Boulder, CU Denver | Anschutz Medical Campus and UCCS — employ more than 26,000 people and contribute more than $6 billion a year to the state economy through spending on goods and services. The university system received $790 million in research funding in 2011 and has spawned 114 companies since the mid-1990s, the vast majority of which still have operations in Colorado.

• Colorado State University in Fort Collins brings in more than $330 million per year for research and employs 7,000 people. In addition, CSU alumni produce $5.2 billion in house hold income in Colorado.

• Collectively, CU and CSU churn out more than 320 new patent filings annually, each one representing even more economic potential.

But dollars aside, those who hunker down in labs for years to unravel scientific puzzles say that the end game is what keeps them motivated: the potential to change lives.

Here’s a look at some of the ways they are doing so.

Riding a wave of cancer discovery

It was June 2009 when Smith, a retired teacher and mother of three, heard the words she had been bracing for since she had been diagnosed with lung cancer 14 months earlier.

“My doctor said, ‘I’m sorry. There’s nothing else we can do for you,’” said Smith, whose left lung already had been removed, and had endured chemotherapy only to see the cancer spread. “The question was: ‘Where do we go now?’”

Smith went to the University of Colorado Cancer Center on the Anschutz Medical Campus.

There she learned of a clinical trial of an experimental drug called Crizotinib, which aims to kill cancer in a way that few other drugs do. It works by inhibiting a molecular mutation or “oncogenic driver” called anaplastic lymphoma kinase (ALK), believed to somehow play a role in turning healthy cells into cancer cells. Only about 4 percent of lung cancer patients (often non-smokers like Smith) possess the ALK mutation, and only they are eligible for the drug. CU researchers helped develop screening tests for ALK and have led the clinical trials on Crizotinib. It earned FDA approval in 2011 and now several other personalized cancer drugs are in the works.

“The paradigm is shifting,” said Dr. Ross Camidge, director of the Thoracic Oncology program at the CU Cancer Center. “If we can screen people for these oncogenic drivers and give them the right drug to interfere with the one they have, we can have a real impact.”

After tests confirmed Smith was ALK-positive, she became one of the first in the world to take Crizotinib.

“By the time I had my next scan, it had reduced the cancer to the point you couldn’t see it any more,” she recalled.

But Smith’s story doesn’t end there.

When the cancer began to crop up again cell by cell, Camidge used targeted radiotherapy to successfully beat it back, a technique he refers to as “weeding the garden.” When the cancer became too aggressive for that, he pulled Smith off Crizotinib and put her on a chemotherapy shown to be particularly effective in ALK-positive patients. Eighteen more months went by. When the cancer reared its head again, Camidge suspected it might have forgotten how to resist Crizotinib, so he put her back on the drug.

Today, Smith is planning a fall trip to Paris with her new husband.

“She illustrates the fact that if you are in a cutting-edge academic center which is involved in new breakthroughs, you can surf a wave of discovery,” said Camidge. “She is still surfing.”

Getting at the root of cystic fibrosis

As a physician who has taken care of plenty of adults with cystic fibrosis, Dr. Jennifer Heinicke knew what lay ahead for her daughter with the disease. When Annelise was born in 2004, median life expectancy for someone with CF was 38; by the time most reached adulthood, they required supplemental oxygen and were probably awaiting lung transplants.

So when Jennifer first got word in February 2012 that the Food and Drug Administration had approved Kalydeco, the first drug ever to treat the underlying cause of the progressive genetic disease, she burst into tears.

“I have seen what a devastating disease this can be,” she said. “To have that not be her future … there are just not words for the kind of gratitude I feel.”

Key to the development of Kalydeco was physician-scientist Frank Accurso, director of the Mike McMorris Cystic Fibrosis Research and Care Center, based at Children’s Hospital in Aurora.

Intrigued by “the puzzle” of a hard-to-understand disease with no cure, Accurso first started studying CF during his residency in the 1970s at the CU School of Medicine. He has since built the CF center into the largest in the country and has played an instrumental role in advancing understanding of CF’s genetic underpinnings.

By the late 1980s, he and his colleagues had zeroed in on a gene called cystic fibrosis transmembrane conductance regulator (CFTR), which when flawed can make it hard for CF sufferers to clear airways of mucus and to digest food.

Annelise must use a special vest 40 minutes per day to help her breathe and takes 25 pills daily to aid digestion.

In 1998, Accurso and the Cystic Fibrosis Foundation partnered with Vertex Pharmaceuticals to use gene sequencing to look for mutations of CFTR. By the mid-2000s they had found one known as the “G551D mutation,” which makes it difficult for sodium chloride (salt) and water to escape cells. Soon they had developed Kalydeco, which essentially “opens the gate” in cells, allowing salt and water to flow as they are supposed to, clearing the lungs.

Accurso led the clinical trials of Kalydeco.

When asked how they went, he still chokes up: “It worked beyond our wildest dreams.”

Today, only about 5 percent of CF patients are eligible for the drug. But researchers continue to work to find other mutations and the drugs to target them.

Meanwhile, Annelise, who started taking Kalydeco on Valentine’s Day 2012, says she can already run further without getting tired.

“She doesn’t necessarily realize what a big deal it is,” Jennifer said. “It could be curative. It could mean that she could have a normal life expectancy and not need a transplant some day. It’s phenomenal.”

Helping farmers flourish

Like farmers everywhere, wheat growers in Colorado have had their share of disasters, from insects to drought. But thanks to an innovative partnership with Colorado State University, the wheat seeds they use each year have improved dramatically, as cutting-edge agricultural research has led to new varieties of seeds that produce more wheat per acre, allow it to flourish in times of drought and make it more resistant to certain diseases.

Dan Anderson is a third-generation farmer in Haxtun about 30 miles east of Sterling, Colo. Anderson sells wheat seed to other growers in the region and his business has flourished because of the high quality of seed stock CSU has developed.

“My brother and I have both been involved in the wheat industry for 20 years,” he said. “We’ve seen these programs grow over time. “

The first varieties that CSU’s Colorado Wheat Research Foundation produced for sale were created in 1996.

“We now have ownership of 15 varieties,” Anderson said. “And these varieties have better yield characteristics, better disease characteristics, and better drought characteristics.”

But Anderson said it’s not just about developing new varieties of seed. CSU is also at work on technologies that may allow them to be developed much faster. Currently it takes seven to 10 years to bring a new variety to market, but that time could be reduced to four years if promising new research at CSU proves to be successful.

“This is a wonderful collaboration between public and private entities,” Anderson said.

Setting the standards
for stuttering therapy

Roughly 1 percent of the American population stutters. Yet just what causes stuttering remains a mystery.

“We are convinced that it is neurologically based and it does have a genetic component, but we are not close to fully understanding it,” said Peter Ramig, a professor in the department of speech, language and hearing sciences at CU-Boulder and a renowned researcher in the field. “At this point, you can’t take away the cause, but you can definitely work around it.”

For 33 years, Ramig has studied the best ways to do that, sharing his findings on therapies not only with patients in his own clinic, but also with speech language pathologists around the globe via textbooks, DVDs and research papers.

He has used computer analysis of stutterers’ vocal cords to better understand why the stutter fades when they change their pitch, as in singing or speaking to a child. He has picked apart the biomechanics of speech — what the tongue and vocal cords do and how air flows when one makes a T or K sound, for instance — and has developed strategies to avoid getting stuck on such sounds. He has also studied the efficacy of hearing-aid type devices for stutterers and was one of the first to explore the impact that self-help groups and desensitization therapies can have on improving speech.

“People understand much better now the importance of dealing with the emotional side of stuttering,” said Ramig, who had stuttered since childhood, but now speaks almost fluently. He stressed that, contrary to popular belief, emotional trauma does not cause stuttering but can exacerbate it.

“When you anticipate that something, like saying certain sounds, is going to be unpleasant, you start to tense and it can make things worse,” he said. “The more you try not to stutter, the worse you get.”

That was the case for Jessica Sabo.

Sabo said she seldom talked at all in high school.

“I didn’t want to hear my stuttering so I would hold it in, and if I did talk, I didn’t want to see people’s reactions so I kept my head down,” she said. “It just created a lot of shame in my life.”

In a brief video that was shot in Ramig’s office 14 months ago, Sabo keeps her head down and eyes on the floor as she struggles quietly for nearly two minutes to form one word.

In subsequent months Ramig urged her to keep her head up and, as she put it, “sweat out the stuttering” rather than hold it in — essentially to desensitize her to the sound of her own words.

“Listening to it changed how I thought about it and how I physiologically reacted to it,” she said.

Sabo does not expect her stutter to disappear entirely, but today she says she has learned to “stutter functionally.”

She is now excelling in her master’s degree program at Naropa University in Boulder, studying counseling and art therapy.

“It has made such a difference to work with someone who stutters,” she said of Ramig. “He knows what it’s like and that has driven his research. He is one of us.”

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