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M.D. News Research Feature | Dr. Robert Recker : "Chance Favors the Prepared Mind"

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“Chance Favors The Prepared Mind”– Madame Curie

One doctor’s referring a patient to another is usually a common occurrence. But most referrals don’t send the physician on a six-year, groundbreaking odyssey, resulting in perhaps the most important discovery in their field in over 40 years. This turn of fate would put prepared minds on an incredible road of research.

Dr. Robert Recker, M.D., and his partner, molecular geneticist Mark Johnson, were dispatched on just such an improbable journey. It began in 1995 when Dr. Recker, chief of endocrinology and the Osteoporosis Research Center at Creighton University, examined a young woman recovering from a car accident. The events from that examination snowballed into a research project where the findings are making waves nationally. They logged many hours, many miles, and tapped nearly every available resource. Their labors paid off well. The full fruit of this discovery could make gigantic leaps in treating osteoporosis, an ever –increasing public health problem affecting 10 million people in the United States, costing $14 billion.

The woman was referred to Recker because her bones appeared to be normal, but had a certain peculiarity. The referring doctor thought Recker should have a look at it. Recker conducted a bone scan of the woman and was amazed. The patient had abnormally high bone density—about 150% denser than normal—with completely normal bone formation. The woman’s mother accompanied her to the visit, and Recker’s amazement turned quickly to curiosity. He performed a bone scan on the mother. The patient’s mother also had incredibly dense bones coupled with normal formation. Dr. Recker had seen nothing like it.

The women’s normal bone formation was the catalyst for further investigation. Instances of high bone density are often paired with an abnormalcy of some kind. So the fact that both women’s bone formation were normal certainly made them unique. The fact the pair were a mother and daughter put it in Recker’s mind there is a hereditary connection. But many questions were to follow and the odyssey was underway.

His first objective was to perform bone scans on all local kindred. That would be hard enough. But to do complete, full-blown research, additional kindred would have to be scanned. Those kindred would be scattered throughout the country. A daunting task, but a large discovery could be waiting.

Ingenuity, the generosity of fellow healthcare colleagues, and the tireless efforts of Johnson and Dr. Recker’s wife, Susan, tempered what they were up against. The trio hit upon a novel idea to gather many kindred members as they could in one location. They hosted a family reunion in Aberdeen, S.D. There they asked to conduct bone density scans and draw for blood. Susan was on the phone a great deal contacting kindred and arranging the reunion, along with checking the obituaries in many different daily newspapers. Johnson would be indispensable while shouldering the bulk of the load in the laboratory doing linkage analysis.

Their research was aided greatly by the kindred’s willingness to help, Recker said. This willingness was even further illustrated by the "need" to have a second family reunion in Omaha. The second reunion largely came about because of a limit in machinery. In Aberdeen, they had used a portable bone scanner. It was difficult to see which kindred exhibited the high bone mass trait because the portable scanner could only scan bones of the upper extremities. Hosting a reunion in Omaha would let Recker have his best tools available to properly scan the attending family members. “"We really bit the bullet on this one. We were operating on a shoestring at the time, but we really needed to have clear information to isolate affected kindred,” Recker said. An added benefit was the research team learned that scans of the bones responsible for body support, such as hips and lower extremities, made finding the trait in any one individual much easier.

The team also benefited from some generosity and a whole lot of trust of a healthcare colleague. In one instance, a subject living in Jackson Hole, Wyo. was afraid to fly to one of the family gatherings. Recker made a call to a friend, and shortly after, a $350,000 mobile unit with a large bone scanner was dispatched from its base in Billings, Mont., to Jackson Hole to scan the family member.

While research was going on, the team had no idea the mutation was to be found on LRP5. LRP5 is a lipoprotein receptor, previously associated with controlling amounts of body fat and cholesterol levels. After DNA samples were taken from all the kindred, they used a marker system that divides the genome into 435 segments. It also uses a heating and cooling system to locate certain fragments. These fragments were then weighed. “The same fragment consistently weighed one weight in the affecteds, and another in the unaffecteds, so that’s where we knew where the territory was,” Recker said. The key was found in the crossovers. “What was there is 15 of the affected individuals was not there in two others that were affected, so we could eliminate that part of it,” Recker said.

In 1997, Recker’s team needed some corporate muscle to get behind their project. They had clear evidence the mutation was happening on chromosome 11, and even had a territory of the chromosome where they thought it might be occurring. It was time they published their findings. “The purpose of publishing that was to see what happened, who we attracted,” Recker said. Among several attracted to it was Genome Therapeutics, based in Woltham, Mass. Genome Therapeutics won out because, according to Recker, “They had good scientists, they were really eager, the contractual arrangements were favorable, and they also had a highly competent gene mapping enterprise.”

Now the area of the entire DNA strand was down to 14 genes, or roughly an area of about 30 centimorgans. Recker’s team, collaborating with Genome Therapeutics, found there was a single base cellular substitution occurring in all the affecteds. “We could tell from the molecule being expressed from the mutant gene, that the gene had a glycine to valine substitution on amino acid 171 out of a string of 1700, which is a difference of about one carbon atom.” Recker said. Without Genome Therapeutics’ help, the process would have taken quite longer than it did. Recker said, “If we had been left to our own crude devices, it would have been years until we found this gene.” The whole process once Genome Therapeutics got involved took about 10 months.

Just how the mutation of LRP5 works is built on the hypothesis that the bone building mechanism in the skeleton is based on a biological meter that has a set point to turn the mechanism on and off. Recker stated that set points are at work in other functions throughout human biology. In the carriers of the mutation, the set point is lower. Under normal conditions the meter reads the skeleton as being under stress, and that triggers the extra bone building, yet keeps the bone formation normal. The lowered meter makes the bone behave as if its being overloaded when in fact it is not, which helps keep the normal formation, Recker said. Now the bigger question lies in determining how the set point works, and finding a way to lower it in people affected by bone thinning. Recker said, We have a treasure trove of experiments and whole host of scientific work we are doing.”

One hypothesis Recker’s team has is a possible connection to osteocites and their attachment to the protein in the bone matrix. Bone builds up in response to stress. Some bending is normal when bone is loaded; it’s the main stimuli for maintaining or increasing bone mass. When stress or tugging happens in the bone, the protein gets bent and then the mass building message could get sent.

This particular mutation of LRP5 takes place in the extra cellular area of the bone cell receptor. Another mutation of LRP5, which is linked to juvenile osteoporosis and early onset blindness, happens in the intercellular part of receptor. Recker said that in laboratory mice, knocking out LRP5 can create the bad mutation, and splicing in the good LRP5 mutation can create the bone- building phenotype. Rather than splicing the gene in humans, a more favorable way to combat osteoporosis would be to lower the set point of a patients’ bone-building meter and let the body build up bone mass by itself. Affecting the set point of the meter might also work positively in the opposite way, combating bad bone formation if it were raised. “There are 15 to 20 congenital diseases that give higher bone mass, but all of them cause derangement. If the skeleton were allowed to build bone willy-nilly, nerves would get crushed, along with improper formation,” Recker said.

Coincidentally, the discovery of the bad mutation on LRP5 was found a short time after Recker found his. Recker describes attending the annual meeting of the National Institutes of Arthritis, Musculoskeletal, and Skin Disease Council that is annually held to disperse research money. Dr. Bjorn Olson was describing to the meeting how an award given to him by the council enabled him to pursue research on a number of families that had a peculiar syndrome of juvenile osteoporosis and early onset of blindness. Olson’s research was linking the syndrome to LRP5. Recker said, “After his speech, I came up to him and said, ‘Bjorn, we’ve got to talk’.” Recker calls this a gene locust—two different mutations happening on the same gene, but doing different things.

Since October 2001, the full story was presented to the American Society for Bone and Mineral Research. In December 2001, Recker and Genome Therapeutics released their study to the American Journal of Human Genetics. Recker has been quite busy since then, juggling invitations to speak, reviewing grant applications of others to research on LRP5, as well as continuing with his research. Recker has been invited to Harvard, the University of California at San Francisco, the University of Illinois, and the University of Wisconsin in the coming weeks. “Everybody wants to hear the story, because it’s a pretty interesting one. It’s really changed the paradigm,” Recker said. The Creighton research team has also identified a couple of additional kindred groups that exhibit the high bone mass trait.

In April 2001, Recker was named a Master of the American College of Physicians. According to a Creighton University press release dated April 4, 2001, “This honor is the highest professional award of the College, which is made up of 115,000 internists. It is the largest organization of physicians in the world. The mastership is awarded to those who have achieved professional distinction in the care of patients, in academic achievement and in professional and ethical standards. The award also recognizes achievement in teaching and science.”

Though a major researcher in his own right, he considers himself a physician at heart. “I like to, and still do, see patients regularly. It gives me an appreciation for what the practitioners do. The primary care practitioners are really the heroes of medicine because they’re out in the trenches and they have a lot of responsibility,” Recker said.

Recker’s relationship with Creighton University has been a long one. After growing up on a veterinary farm in south central Nebraska, he began his higher education at Creighton in 1956. He received his undergraduate and medical degrees from Creighton, and completed his research fellowship in Endocrinology and Metabolism at Creighton University Medical School.

Since beginning at Creighton, he has only been away for a five-year military career in the Air Force. He completed a medical internship at an Air Force hospital at Lackland Air Force base in Texas, and was a flight surgeon while serving. Recker has been on the teaching staff at Creighton Medical School since 1971, has been the director of the Creighton University Metabolic Research Unit since 1974 and Creighton’s Osteoporosis Research Center since 1986. Recker oversees a staff of nearly 70 full time employees at the center. He is also currently the president of the American Society of Bone and Mineral Research, which has around 5,000 members.

Recker says that one of the ways to be successful in research is to stay at it for a long time in the same area. In the field of human research, “There’s a big value of being known in the area and have people have a favorable view. You can’t get people to volunteer for human research unless you are really nice to them,” Recker said. It has paid off because over the years, he has compiled an archive of over 15,000 patients and research subjects. Recker said, “I’ve been persevering and having fun all these years.”

First Westroads Bank Feature 

Head: They're Not Your Ordinary Bankers

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Imagine this: Your day starts with hospital rounds. By 8:30 you're in your office, ready to see your first impatient patient. If there is a lunch break, it's catch up time. In the afternoon, it's more patients and paperwork. You bolt from the office to a meeting and then if you're lucky, you make it to the musical at the high school where your daughter has the lead role just as the curtain goes up. Sound crazy? Sound familiar? It does to most physicians. It doesn't leave much time to breathe, let alone bank.

First Westroads Bank knows how tough a physician's schedule can be. And, not being ordinary bankers, FWB staff believes banking should be the last thing physicians have to worry about. These bankers take valuable hints from the medical profession in their approach to business. A doctor-patient relationship should be long-lasting and rewarding. So should a banking relationship. First Westroads Bank makes customers feel comfortable and earns their trust. And they make banking simple and convenient.

First Westroads Bank, chartered in 1967, currently has over $140 million in assets. The Bank has received a number of prestigious awards, among them recognition as ranking 10th out of nearly 4,000 banks in the Midwest by the SNL Securities publication, Strategic Advisor. First Westroads Bank was identified by the American Banking Association in the ABA Banking Journal as one of the “50 Best Community Banks” in the country. The U.S. Small Business Administration also named First Westroads Bank as one of the top small business lenders.

First Westroads Bank Chairman and CEO Chris J. Murphy grew up around physicians, and that left a lasting impression on how his bank does business. His father was a pediatrician who practiced for 47 years. “Growing up in a physician’s family has made me appreciate that physician’s time is very valuable, and tailoring financial products to their needs is the premise we’ve built our program on,” he said.

Murphy knows what a young doctor just beginning a medical practice will need, and he and his executives have the proper outlook to help them succeed. “The time physicians need a bank most is when they’re first starting. They generally need assistance with cash flow, buying a home, and auto and school loans,” Murphy said. The bank also looks to a physician’s future. Murphy knows young professionals just completing residencies need a bank that is able to work with them. Adds President and Chief Lending Officer Stephen F. Robinson: “As these physicians come out of residencies, they often have acquired considerable debt while completing their education. As a banker, you have to be able to look forward — to their potential in the future. We do that. I think that is a necessary part of building a relationship with physicians and helping them at the time they really need it.”

First Westroads Bank carries their understanding through every level of a professional’s career and beyond. Murphy states, “It’s the bank’s philosophy in dealing with all of our customers. We appreciate physicians and their financial needs. Some institutions might be less knowledgeable of those needs and just look at preliminary figures and say, ‘No, your loan request doesn’t meet our policy guidelines,’ versus our philosophy, with not only physicians, but with all of our customers. Because we’re a relationship bank, we focus on the needs of our customers, and then meet those needs quickly.”

Vice President and head of Professional Banking James S. Follon explains how quickly First Westroads acts. He said, “We have quick turnaround time because all the decision makers are in one place. The CEO, president, and vice president are near one other and can make a decision on any loan within 24 hours.” Murphy relates this ethic to how good medical care doesn’t wait for everyone’s schedule to connect. “Our philosophy is once we have the information we need, we will call a meeting of our loan committee. It’s the same way that physicians practice — they don’t put off meeting on important care issues, because patients need decisions made quickly.”

Convenience plays a big role, too. First Westroads Bank achieves ultimate customer convenience in a number of ways. The bank offers MobileConnect, a deposit courier service where a bonded and insured courier picks up deposits at a business customer’s office. The service acts as a mobile bank, like house calls made by physicians in the past. The First Westroads Web site also features a complete business banking section. Follon says, “It’s not just a consumer banking service we’re trying to convert to business. Its focus from the start was to benefit the business customer. Instead of building more branches, we try to build relationships.” Adds Robinson, “Banks have different methods of delivery. Our method has worked well for us. It’s been a very successful way of offering branch facilities to our customers. Between our Web-based business banking and our mobile service, I don’t know how banking could be any more convenient.” This type of convenience literally means that First Westroads’ nearest location is in your office.

First Westroads even boasts onsite Investment Center employees who offer full investment services and other financial planning, including retirement, college, and estate planning. With Investment Center staff situated firmly inside the Bank, customers don’t have to go elsewhere to receive these services.

For physicians, this kind of convenience allows them to utilize good time management. Robinson said, “Most physicians are very busy and their schedules are intense. Perhaps they don’t have as much time to dedicate to their banking relationship as they’d like to. We’re here to help them alleviate that problem. We take the service to them rather than having them come to us. We’ve been very proactive in going to them and offering them relationship services, versus them having to ask us for that. With their time constraints, I think physicians need and want our services.”

Accessibility is another business principle at First Westroads. Bank employees are easy to reach and always eager to assist. Murphy said, “Our hours are not 8 to 5; they are when the customer needs us. For example, there was a medical administrator who was looking to recruit a physician specialist. Part of that recruitment process was the ability to obtain a home that the couple could see during a weekend here. Aadministrators often ask us to meet with a couple on a Saturday morning at the Bank before they go out and look at houses and to be ready to assist them with a quick turnaround on a home. That’s trying to be there when the need is, and it also helps the physician group attract someone who might be looking at several cities, and the Bank can be part of their recruitment process.

“Accessibility also means extending customer service, personally talking to customers, and sharing our expertise with them.” Follon said, “We have a high degree of understanding the problem and solving it. A lot of times in business, people just talk to you long enough to get you to the next person.” Murphy adds, “The banking business from the lending standpoint is a commodity — the color of our money is the same as everyone else’s. In order to differentiate ourselves, we have to add value. Physicians have told us they want to be able to call and talk to a decision maker. And they’d also like to get an answer — yes or no — quickly. On that basis, First Westroads Bank has devised a process to meet those needs.”

Good financial care comes with customer service and expertise that walks the walk. Follon said, “I think we have the strongest expertise of years of experience of any bank in the city. And, we have a broad understanding of all banking situations.”