Allan I. Pack, MBChB, PHD, and Raymond J. Galante, basic science lab manager for the Center for Sleep and Respiratory Neurobiology at the University of Pennsylvania.

This past March, Allan I. Pack, MBChB, PhD, founder and director of the Center for Sleep and Respiratory Neurobiology (CSRN) at the University of Pennsylvania Medical Center, received a lifetime achievement award from the National Sleep Foundation (NSF) honoring his invaluable contributions to the field. Pack has long been known for his tireless dedication to the advancement of sleep medicine&#8212but he is quick to acknowledge that 20 years ago, his career could have taken an entirely different turn.

In 1989, Pack found himself at a crossroads after being passed up for a key promotion to head the pulmonary division at the University of Pennsylvania (Penn). Just the year before, Pack had secured one of three federal grants through the National Institutes of Health (NIH) to start a sleep research center at the university. But even though Pack, who came from a pulmonary background, was emerging as one of the top professionals in the field of sleep medicine, the chair of the search committee confessed that he didn’t see the value of the discipline.

“He said, ‘You could say you were great, but who needs your field?’” Pack recalls.

Unsure of his next move, Pack consulted with Norman H. Edelman, MD&#8212then the dean of the Robert Wood Johnson Medical School in New Brunswick, NJ&#8212who advised him to view his situation as an opportunity. He suggested that Pack model his career on that of William C. Dement, MD, who founded the world’s first sleep laboratory at Stanford University in California and laid much of the groundwork for the fledgling field.

“He said, ‘You should try to become the Bill Dement of your time,'” Pack recalls. “I don’t believe I ever did that, but it was an important guiding principle for me.”

Inspired, Pack went back to Penn and modeled his approach to sleep medicine on Dement’s example.

“Bill understood that the driver for the field wasn’t money; it was new knowledge,” Pack says. “New knowledge helps our patients and creates opportunities for practitioners in terms of new diagnoses and treatments. Second, Bill always looked at what was best for the field of sleep medicine. Last, Bill was extremely passionate, and he never quit. So, I’ve always tried to live up to these principles.”

Since that time, Pack&#8212who has served as the director of the CSRN for 18 years&#8212not only has been instrumental in building one of the most respected sleep research centers in the world, but he also has become one of the field’s top researchers, educators, and advocates.

BUILDING A DREAM

Not long after Pack’s conversation with Edelman, William N. Kelley, MD, became the new dean of medicine at the University of Pennsylvania and CEO of the University of Pennsylvania Health System. Kelley removed the chairman of medicine who had passed over Pack during the promotion process. Then, he asked Pack what it would take to keep him at the university. When Pack drew up a proposal to run his own sleep center, Kelley enthusiastically accepted and agreed that Pack would report directly to him.

“That’s how the first medical-school-wide sleep center in the United States was created,” Pack says.

From the beginning, the CSRN was an interdisciplinary endeavor.

“We felt that sleep was a multidisciplinary area, and that it should not be housed in just one school of the university or in just one department of one school,” says David F. Dinges, PhD, professor of psychology in psychiatry, chief of the division of sleep and chronobiology in the department of psychiatry, and associate director of the CSRN. “So, we all worked very hard to try to make sure that there were sleep scientists, including circadian scientists, in all of the schools at Penn, wherever possible.”

Recruiting researchers with relevant expertise to sleep medicine became a key part of the job for Pack. For example, he persuaded Amita Sehgal, PhD, then an assistant professor in the department of neuroscience who was studying the clock molecules in Drosophila, to study sleep in the fruit flies as well. He also convinced Ted Abel, PhD, who is in the biology department in the School of Arts and Sciences, to think about the effect of sleep deprivation on memory at the molecular level. Abel studied mechanisms of memory.

“I saw that as my job,” Pack says. “I did my own science, but I attracted people to join in from various departments. Once we got enough momentum from that, I was able to persuade department chairs to go out and recruit people specifically for sleep.”

Emmanuel Mignot, MD, PhD, professor of psychiatry and behavioral sciences and director of the Center for Narcolepsy at the Stanford School of Medicine, notes that the multidisciplinary nature of the CSRN serves as a model for how sleep medicine should be incorporated into other universities.

“[Pack] doesn’t see the sleep field as something that should be controlled only by sleep people,” Mignot says. “He has a very open and free model in trying to engage people outside of the field.”

Although the CSRN got off to a promising start, the clinical program began to lag in the 1990s due to a lack of resources. “I couldn’t get new clinical faculty, and the hospital wouldn’t give us new resources,” Pack says. “As a result, our waiting time for a sleep study grew to 6 months.”

The survival of the research program depended on reducing the long wait for patients. So, in 2001, Pack was able to move the clinical program out of the pulmonary division and make it a separate entity. He also outsourced the business management aspects of the clinical laboratories to a third-party company, which meant Pack’s team was no longer burdened with the bureaucratic demands of the health system and could focus all of their efforts on building the program itself.

“Over about a 5- to 7-year period, we grew our clinical program fivefold, in terms of both patients we saw and also the studies we were performing” Pack says. “Now, we’re continuing to build high-quality clinical centers across the Delaware Valley region.”

The result is a program that thrives in both the clinical and the research realms. “Allan has established this interdisciplinary center as one of the largest and highly regarded sleep centers in the world,” says Clete A. Kushida, MD, PhD, RPSGT, acting medical director of the Stanford Sleep Disorders Clinic, director of the Stanford Center for Human Sleep Research, and associate professor at Stanford University Medical Center, who recently worked with Pack through the Academic Alliance for Sleep Research.

Pack credits this success to perseverance. “We did not do this overnight,” he says. “We had a vision of what we were trying to do, and we just kept going to implement that vision. It has really taken us from the mid 1980s until now to see the whole thing come into full fruition.”

FURTHERING SCIENCE

Pack not only is celebrated for his role in building the CSRN, but he also has made significant contributions to scientific research.

“Allan is a pioneer in the field of molecular mechanisms of sleep and sleepiness and is a recognized expert in the pathogenesis of obstructive sleep apnea,” Kushida says.

Dinges notes that Pack has been instrumental in cementing the importance of sleep science to the NIH, particularly through his long and successful track record of funding through the National Heart, Lung, and Blood Institute.

“He has helped spearhead the area of apnea research&#8212understanding apnea, the mechanisms of apnea, the consequences of apnea, and the prevalence of apnea&#8212and that has been a major tour de force,” Dinges says. “He has also helped the clinical sleep field move into the area of genetic contributors to apnea and the basic mechanisms of apnea.”

As a result, Pack’s research has also been a key factor in raising the profile of sleep science&#8212both in the scientific community and in the general public.

“It was critical during the 1980s and 1990s to establish sleep science as a credible area of science,” Dinges says. “Allan was certainly one of the leaders in that effort.”

Pack’s most influential research in the past decade has been the exploration of sleep-like states in nonmammalian systems. In 2000, he helped author a paper with Joan C. Hendricks (now the Gilbert S. Kahn Dean at Penn’s School of Veterinary Medicine) and Sehgal for Neuron that demonstrated that there is a sleeplike state in the fruit fly, Drosophila. The idea was to build on research that explored abnormal clock times in Drosophila to see how it applied to sleep.

“Drosophila is a wonderful model to find genes regulating sleep, and several labs in the country that studied clock genes are now studying sleep in Drosophila,” Pack says.

In 2008, his postdoctoral fellow, David Raizen, published a paper with Pack in Nature that described a sleeplike state in the Caenorhabditis elegans worm.

“The worm has got only 302 neurons, and all the connections are known,” Pack says. “So, it is a very powerful system for studying the molecular bases of behavior.”

Pack believes that these two papers have been his most important in the past 10 years because they have opened up opportunities for new research.

BUILDING AWARENESS

In the early 1990s, Allan I. Pack, MBChB, PhD, founder and director of the Center for Sleep and Respiratory Neurobiology (CSRN) at the University of Pennsylvania Medical Center, took a sabbatical to serve as unpaid medical director for the fledgling National Sleep Foundation (NSF). During his tenure, he strongly advocated for a national drowsy-driving awareness campaign.

The NSF began by creating a drowsy-driving awareness program for the state of New York’s first sleep awareness week. The symposium was so successful that the governor’s traffic safety representative approached Pack about the possibility of creating statewide initiatives.

The following year, New York’s then governor, Mario Cuomo, established a drowsy-driving task force. Pack served on the task force, which was instrumental in building safe rest stops and installing rumble strips on New York’s freeways.

“It became a model program,” Pack says. The NSF went on to sponsor a national meeting on the topic that was covered by all of the major networks.

“We put a report together about rumble strips that was then distributed to all of the states,” Pack says. “That led to very widespread implementation of rumble strips on all of the major roads.”

After Pack returned to the University of Pennsylvania, the NSF continued to be active in building drowsy-driving awareness campaigns. Although Pack notes that it has been surprisingly difficult to fund initiatives in this area, the NSF is still taking steps to build awareness, such as focusing on drowsy driving prevention and awareness during a recent national conference.

Pack says the NSF’s efforts have succeeded in building awareness throughout the country.

“They’ve continued to make progress,” Pack says. “In the early 1990s, fewer than five states even had a box labeled ‘fell asleep’ on the crash-report form&#8212now, almost all of them do.”

“Amazingly, there are three labs already studying sleep in C. elegans,” he says. “There was also a meeting on nonmammalian models of sleep earlier this year at the Howard Hughes Institute. All of that is totally new.”

Currently, Pack studies mice and Drosophila in an effort to discover the genes regulating sleep. This research also feeds into his long-time curiosity about the mechanisms of consequences of sleep apnea.

“I’ve always been fascinated, not just about sleep apnea itself, but with sleepiness,” Pack says. “In other words, what goes on in your brain when you’re very, very sleepy?”

In his human research, Pack continues to look for the root causes of sleep apnea. Along with Thorarinn Gislason, MD, PhD, FCCP, of the University of Iceland, and deCODE Genetics, he secured a grant to study the sleep-study data and DNA of 3,500 patients to try to find the genes that are responsible for sleep apnea. “We’re making real progress in that,” Pack says.

Pack is also involved in researching biomarkers&#8212signals in the blood&#8212that may indicate sleep apnea or the potential to develop cardiovascular consequences from sleep apnea.

“Allan is always very enthusiastic about moving the field forward,” Mignot says. “He’s really a big-picture person, and he’s always on the forefront of what is going to be important.”

Pack is also known for encouraging the research of others in the field, particularly the endeavors of junior faculty members. Nathaniel F. Watson, MD, assistant professor of neurology and codirector of the HMC Sleep Disorders Center at the University of Washington in Seattle, is in year four of a K-23 award from the National Heart, Lung, and Blood Institute. He is studying sleep duration in twins, and he credits Pack with helping him both hone his focus and secure funding for his research.

“The remarkable thing about Allan is that he not only is an important mentor to those at his institution, but he also reaches out to junior faculty at outside institutions in order to help them reach their research career goals,” Watson says. “His infectious enthusiasm, his advocacy for sleep medicine, and his desire to mentor the next generation of sleep researchers have moved the field of sleep medicine forward in ways that I think we won’t fully appreciate for many years to come.”

LOOKING AHEAD

As the emphasis in health care moves toward personalized medicine, Pack sees exciting changes ahead in the field of sleep medicine&#8212particularly as research in genetics and biomarkers progresses.

“It’s a very exciting field, and it’s in its infancy,” Pack says. “I think when you come back in 20 or 30 years, sleep medicine will look very different than it looks today.”

While he acknowledges that reimbursement concerns are very real for those starting in the field, he notes that there is unprecedented demand for sleep medicine that will create many opportunities. “It is a time of enormous clinical need,” Pack says.

Part of addressing this need is thinking creatively about sleep&#8212and that means working collaboratively with professionals in all different fields.

“Allan has been passionate about creating a nationwide network of sleep researchers, and he really is working tirelessly to improve collaboration among different institutions,” Watson says. “I think he appreciates that in today’s modern research world, only through collaboration can we really answer some of the bigger questions facing sleep.”

Pack believes that sleep professionals should focus every effort on reducing death and disability due to sleep disorders and sleep deprivation. The way to do this, he says, is through good science that informs public policy and by focusing clinical programs on excellent outcomes.

“My own view is that sleep is not a diagnostic discipline,” Pack says. “Our future is to show that we can get enhanced outcomes of care. At the end of the day, we need to be a field that changes people’s lives.”

Ann H. Carlson is a contributing writer for Sleep Review. She can be reached at [email protected].