Can We Turn Back the Clock on Aging? Senolytic Drugs Keep People Healthy Longer by Disrupting the Aging Process
UNIVERSITY OF MINNESOTA MEDICAL SCHOOL SPRING 2019
PAGE 10 Can we turn back the clock on aging? Senolytic drugs keep people healthy longer by disrupting the aging process
15 Preparing Native students 20 NK cells versus 24 The art and science 36 Pushing the limits for medical careers ovarian cancer of diagnosis in MR imaging
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PAGE 36 Still pushing the limits
A world leader for four decades, the U’s Center for Magnetic Resonance Research continues to raise the field to higher levels
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IMAGE: COURTESY OF JEFFREY WOZNIAK, PH.D. OF JEFFREY WOZNIAK, COURTESY IMAGE: 10 Can we turn back the clock on aging? U scientists are discovering drugs that keep people healthy and vibrant longer by disrupting the aging process
15 Points of pride Nationwide, schools still struggle to draw Native Americans and Alaska Natives into medical careers; here’s what’s working 10 at our Medical School’s Duluth campus
20 Going cell-to-cell with ovarian cancer Masonic Cancer Center researchers evaluate a unique immuno- therapy designed to keep this wily disease from coming back
24 Getting it right How doctors in training can learn to avoid making the wrong diagnosis
ALSO IN THIS ISSUE MORE ONLINE
2 Medical School News Visit medicalbulletin.umn.edu to find web-only content and 8 Global Outreach 15 the online edition of the A social perspective Medical Bulletin. on medicine
28 Alumni Connections
28 Alumni Spotlight Prescribed reading Email us at [email protected] for young patients to receive the Medical Bulletin by email instead of as a 30 Scholarship Winner paper copy. Coast Guard duty serves her well
35 In Memoriam
36 A Look Back U’s imaging center 20 still pushes the limits
FIND THE MEDICAL BULLETIN ONLINE AT: medicalbulletin.umn.edu
Cover illustration by Hanna Barczyk
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Moving up A good decision is based on AS WE WRAPPED UP the Medical School’s 130th anniversary at the close of 2018, years of effort began to bear fruit. We are delighted to see significant knowledge and not on numbers. improvement in our national rankings. Our Blue Ridge ranking, which mea- – Plato sures the amount of National Institutes of Health research funding awarded to our Medical School, rose from No. 33 in 2017 to No. 30 in 2018. Medical school rankings are This improvement represents millions of successfully competed for one indicator of an institution’s dollars and thousands of hours of work that will eventually result in medical perceived quality. advances. Likewise, our 2020 U.S. News & World Report best medical schools research ranking improved, moving up to No. 43 from No. 46. We are also – U.S. News & World Report making progress in education and training, as reflected in our U.S. News primary care ranking, which climbed two spots to No. 10. Notably, our family medicine specialty came in at No. 5. Rankings are just numbers, but the numbers convey a message about our institution and its reputa- tion. We have renewed our commitment to do the work required to better serve our patients, our students, and our community.
HERE ARE A FEW HIGHLIGHTS: We have hired impressive new faculty to join our Medical Discov- PHOTO: BRADY WILLETTE BRADY PHOTO: ery Teams, which are working to address complex health prob- lems profoundly affecting Minnesotans by delving into the biology of aging, addiction, rural and American Indian health, and optical imaging and brain science. I have asked several Medical School faculty members to assume broader responsibilities as associate deans, creating more con- nectivity between leadership, faculty, staff, and students by dis- tributing responsibility and authority. Find the current list of leaders at med.umn.edu/about/leadership. Last, but certainly not least, our teams are now working to opera- tionalize the new M Health partnership with Fairview Health Ser- James Hereford, Fairview president and CEO, and Jakub Tolar, M.D., Ph.D., Medical School vices. Among the partnership’s key features are greater financial dean and vice president for clinical affairs support for academic medicine and academic physician leadership through- out the system. University of Minnesota Physicians, now led by CEO Badrinath Konety, M.D., M.B.A., remains an independent organization. Aligned with the University’s land-grant mission, it will work with other partners and maintain the U of M brand in the market. Additionally, the University and Fairview are working together to create a Wellness Alliance with the goal of restoring well- being and joy to the practice of medicine.
Right now, we are in the early days of putting the plans for our Joint Clinical Enterprise into practice. I look forward to providing future updates on this critical partnership.
Jakub Tolar, M.D., Ph.D. Dean of the Medical School and Vice President for Clinical Affairs
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New cancer drugs tell UNIVERSITY patients when it’s time OF MINNESOTA MEDICAL SCHOOL for a pill Jakub Tolar, M.D., Ph.D. There’s an app for almost anything these Dean days — even cancer care, thanks to a tech- TWIN CITIES CAMPUS nology that can help to optimize at-home cancer treatment. Anja Bielinsky, Ph.D. Associate Dean for Foundational Science Experts from University of Minnesota Colin Campbell, Ph.D. Health and Fairview Health Services recently TRIBUNE 2019, STAR COPYRIGHT BRIAN PETERSON, PHOTO: Associate Dean for Graduate Education partnered with Proteus Digital Health to bring Denis Clohisy, M.D. a new type of pharmaceutical called digital Associate Dean for Surgical and medicine to people being treated for cancer. Procedural Specialties Digital medicine is already being used in Susan Culican, M.D., Ph.D. An ingestible capsule containing a digital sensor and the treatment of conditions like diabetes and Associate Dean for Graduate chemotherapy medication allows doctors to monitor Medical Education hypertension, but the M Health team is the their patients’ at-home cancer treatment. first in the world to use it for cancer. Robert Englander, M.D., M.P.H. Associate Dean for Undergraduate Here’s how Proteus Discover technology Medical Education works: A pharmacist puts an ingestible, FDA- Taking oral chemotherapy medicine at Badrinath Konety, M.D., M.B.A. approved sensor and prescribed chemother- home can be easier for patients, but it also Vice Dean for Clinical Affairs apy into a small capsule. The patient wears can be challenging, Greeno says. Peter Mitsch a patch on his or her torso that syncs to a “If a patient doesn’t feel well, for example, Chief Financial Officer secure app. When the patient swallows the that person might intentionally decide to skip Dimple Patel, M.S. capsule and it reaches the stomach fluid, the a pill or take an extra dose,” he explains. “This Associate Dean for Admissions sensor sends a signal to the patch. The patch can be problematic when taking oncology Mark Rosenberg, M.D. records the time the patient took the medi- drugs. It’s also possible Vice Dean for Education and Academic Affairs cine, as well as the patient’s heart rate and for a patient to misun- Patients can see when Timothy Schacker, M.D. activity patterns. This information is sent to derstand the instruc- they took their medication Vice Dean for Research the app, which is visible to the patient, his tions for their drugs and get reminders before Amanda Termuhlen, M.D. or her care team, and, optionally, a support and accidentally take Associate Dean for Faculty Affairs network of caregivers. them incorrectly.” their next dose. They can Bevan Yueh, M.D., M.P.H. “We’ve put a lot of time and thought into Proteus Discover also report any problems Associate Dean for Strategy and Innovation creating safeguards for chemotherapy over can help to avoid some directly to their doctors the years,” says the University of Minnesota of these problems. DULUTH CAMPUS Medical School’s Edward Greeno, M.D., also Patients can see when through the app. a hematologist/oncologist for University of they took their medica- Paula Termuhlen, M.D. Regional Campus Dean Minnesota Health, who helped to implement tion and get reminders before their next dose. Raymond Christensen, M.D. the digital medicine program for cancer They can also report any problems directly to Associate Dean for Rural Health patients. “Digital medicine gives us the their doctors through the app. Catherine McCarty, Ph.D., M.P.H. chance to provide safety oversight when a “It’s an additional tool I can use to keep Associate Dean for Research patient takes oral chemotherapy from home, my patients as healthy as possible and avoid Robin Michaels, Ph.D. M|B which leads to better outcomes.” potential problems,” Greeno says. Associate Dean for Student Life and Academic Affairs
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Robots help U researchers detect autism earlier
UNIVERSITY OF MINNESOTA researchers plastic, making it easier are turning to robots to help children with to change the course of autism spectrum disorder benefit from development. early interventions. In the group were Maria The researchers, from the Medical School Gini, Ph.D., previously and the College of Science and Engineering, professor of computer Talking robots can help to reveal early signs of autism spectrum disorder. are using moving, talking robots that interact science and engineering; with children ages 2 to 4 years old and gather Marie Manner, Ph.D., formerly a student in data that can reveal early signs of autism. One computer science; Amy Esler, Ph.D., assistant way, Gini says, they avoid any bias that a in 59 U.S. children is on the autism spectrum, professor of pediatrics; and Suma Jacob, M.D., human might bring into the assessment. but most aren’t diagnosed until age 4 or 5. Ph.D., associate professor of psychiatry and “Autistic children like to interact with tech- Earlier detection pediatrics. nology more than with people,” she says. “The gives health pro- The robot is a tool for seeing how children objective of the project is to diagnose autism WEB EXTRA fessionals more interact with their surroundings and collect- when the kids are very, very young, because See the robot in opportunities to ing large amounts of data that can help the intervention can be done earlier, and it’s action at z.umn.edu/ start treatment experts make more accurate decisions about much more effective.” M|B ASDrobot. when children’s the presence of autism-like symptoms. And brains are most because the robots behave in a standardized
New device could change concussion diagnoses
Diagnosing concussions and other traumatic The EyeBox detects signs of concussion The movements allow doctors to assess the brain injuries can be tricky. Current tests don’t by tracking patients’ eye movements as nerves in patients’ eyes, which are sensitive produce reliable yes-or-no results and are sus- they watch a four-minute video. to potentially elevated intracranial pressure, ceptible to manipulation by patients looking a telltale symptom of a brain injury. to avoid a brain injury diagnosis — such as After years of clinical testing, EyeBox was athletes who want to return to play as soon approved by the U.S. Food and Drug Admin- as possible. istration in early 2019 and will be available COURTESY OF OCULOGICA COURTESY IMAGE: But a new device created by Uzma Sama- for physician use from the biomedical com- dani, M.D., Ph.D., a neurosurgeon with Henne- pany Oculogica. pin Healthcare and an associate professor of “Really what we are talking about is neurosurgery at the University, could change changing the way brain injury is diagnosed how concussions are identified by providing and defined,” Samadani told the Star Tribune doctors with quantifiable data, making the in January. M|B diagnosis process much more clear. The device, called EyeBox, detects signs The device allows doctors to assess whether of concussion by tracking patients’ eye move- eye nerves show signs of increased intracranial ments as they watch a four-minute video. pressure, a telltale symptom of brain injury.
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U investigators nd a new way STUDY LINKS INFECTION to attack two high-risk viruses WITH HEART ATTACK
Researchers from the University of Minnesota, the Howard Hughes Medical AND STROKE Institute (HHMI), and the University of Toronto have discovered a possible path High blood pressure, diabetes, high cholesterol, toward preventing the development of cancers tied to two viruses that infect and tobacco smoking are well-known, long- millions of people around the globe each year. term risk factors for stroke and heart attacks. Published in Nature Microbiology, the research focuses on how the Epstein- But when it comes to short-term risk, other Barr virus (EBV), most commonly known for causing mononucleosis, and factors might be at play, according to new Kaposi’s sarcoma herpesvirus (KSHV) research from the University of Minne- shield themselves from destruction sota Medical School and School of Public inside the human body. Health. The study, published last November in “People infected with EBV or KSHV will the Journal of the American Heart Association, have the virus for life,” says Adam Cheng, shows that certain infections, such as those in a Medical Scientist Training Program stu- the lungs (pneumonia) and urinary tract, can dent at the University of Minnesota Medi- increase the risk of heart attacks and stroke cal School and the study’s lead author. “In by acting as “acute triggers.” most cases, the virus will remain dormant. Led by Kamakshi Lakshminarayan, Ph.D., However, sometimes these viruses can an assistant professor in the Department of DR. GOPAL MURTI/SCIENCE SOURCE MURTI/SCIENCE DR. GOPAL IMAGE: reactivate and lead to abnormal, cancer- Neurology, the study found that infections ous cell growth. But now, in the wake of substantially increased a person’s short-term our research, data suggests it may be pos- risk of having a heart attack or stroke. For sible to suppress the virus indefinitely.” example, in the two weeks after an infection Under ideal conditions, a human DNA requiring hospitalization, a patient’s heart enzyme called APOBEC3B is capable of Magnified and colored transmission electron attack risk increased by 13-fold, and the odds micrograph of Epstein-Barr virus mutating and killing EBV and KSHV as of a stroke increased sixfold. they invade and replicate inside the body. “The key to explaining the association However, researchers discovered that both viruses are able to produce defense between acute infections and the short-term proteins that bind directly to the APOBEC3B enzyme. When they do, APOBEC3B increased risk of strokes and heart attacks is unable to mutate and kill the viral DNA. is inflammation,” Lakshminarayan says. “Our work suggests that by blocking the viruses’ defense proteins, it may “Inflammation promotes plaque buildup in
OCULOGICA be possible to treat mono and prevent the development of cancers caused blood vessels and also increases the tendency
OF by EBV and KSHV,” says senior author and Masonic Cancer Center member of these plaques to rupture, thereby blocking Reuben Harris, Ph.D., who is an HHMI Investigator. “The viral defense proteins blood vessels.”
COURTESY are excellent targets for drug development.” Logan Cowan, a School of Public Health Meanwhile, the U’s Henry Balfour Jr., M.D., a professor in the Medical School’s doctoral student involved in the research, IMAGE: departments of Laboratory Medicine and Pathology and Pediatrics, is working says the findings underscore the importance on bringing an experimental vaccine for EBV to the public. Balfour and his team of infection prevention and education. believe that a vaccine that prevents EBV also holds the potential to prevent “Infection prevention is key — so vaccination mono and other diseases EBV has been linked to, including a variety of cancers for influenza and pneumonia is important,” and multiple sclerosis. M|B he says. “Perhaps we should also consider infection as a ‘treatable moment’ during which cardiovascular preventive strategies should be implemented.” M|B
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External funding for U research reaches record level
The University of Minnesota announced in December that it success- fully competed for a record $793 million in external research funding in fiscal year 2018. That’s according to the 2018 Annual Report on Research and Technology Commercialization released by the Univer- sity’s Office of the Vice President for Research. The University ranked ninth among the country’s public research universities in research expenditures, according to the most recent Experienced coaches offer National Science Foundation Higher Education Research and researchers individualized Development Survey, which compared research expenditure data business advice. collected from fiscal year 2017. The Twin Cities campus expended
PHOTO: HOLLY SANTIAGO, OFFICE OF THE VICE PRESIDENT FOR RESEARCH $922 million on research in that period, while the five-campus system expended $948 million. New incubator helps U launch startups OTHER HIGHLIGHTS FROM THE REPORT:
RESEARCHERS AT THE University Discovery Launchpad 6.5 percent growth in the University’s external research portfolio over fiscal year 2017 of Minnesota have a new resource provides expert on campus to help them bring 12.7 percent increase in federal awards their discoveries beyond the lab coaching and support and into the marketplace. for researchers who are 17.7 percent increase in state awards The Discovery Launchpad is an interested in forming incubator program developed by 8.8 percent increase in National Institutes of Health a startup company the U’s Venture Center to provide funding ($22 million) over the previous year expert coaching and support for to commercialize 51 percent of all fiscal year 2018 research awards researchers — including those from new technology. were to the Medical School or other health the Medical School — who are sciences endeavors interested in forming a startup company to commercialize new technology. $42.6 million grant — one of the U’s largest federal grants The program connects researchers with advisers who coach ever, from the NIH National Center for Advancing them through the process of creating business, marketing, and sales Translational Sciences — to be distributed over plans, as well as working on financial management and developing five years for the University’s Clinical and Transla- a business pitch. tional Science Institute, which helps to move lab “By offering individualized advising from experienced executives discoveries into clinical practice faster M|B and entrepreneurs, we can improve the success of new startup com- panies based on U of M research, bring new technologies into the market, and increase the overall return on investment for research,” WEB EXTRA says Russ Straate, associate director of the Venture Center. M|B To view the 2018 Annual Report on Research and Technology Learn more about the Discovery Launchpad Commercialization, visit z.umn.edu/ResearchAR. at z.umn.edu/discovery-launchpad.
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More U students reporting mental health concerns U RECEIVES $5.4M The number of students coming to college TO ADDRESS MEDICINE with mental health concerns continues to SHORTAGES increase, according to results from a recent The U’s Center for Infectious Disease health survey of students on the University Research and Policy (CIDRAP) has of Minnesota’s Twin Cities campus. received a $5.4 million gift from the Slightly more than 42 percent of current Walton Family Foundation to address students reported having a mental health global drug and medical supply shortages. diagnosis in their lifetimes, a 29 percent CIDRAP’s work will focus on the supply increase since 2015. The increase was par- chains and global disruptions for drugs ticularly significant for female students, that provide lifesaving and life-sustaining with almost half reporting a mental health treatment, with the goal of improving the condition in their lifetimes compared with system’s ability to maintain a steady and 39 percent in 2015. adequate supply of these critical medica- The data come from the 2018 College Stu- tions and supplies worldwide. CIDRAP is dent Health Survey of University of Minnesota “As student mental health needs grow, we a global leader in addressing public health Twin Cities students, directed by the U’s have to ask what resources will be needed to preparedness and emerging infectious Boynton Health Service. keep pace,” he says. “The scale of our campus disease response. Gary Christensen, ’86 M.D., Boynton’s chief puts us in a better position to provide students Unexpected yet significant shortages medical officer, says the survey helps U lead- a range of resources. But all colleges and uni- in medical supplies are often due to man- ers identify health issues affecting students versities are struggling to keep up. Our survey ufacturing disruptions caused by natural and gives them valuable information to create should be a clear sign to policymakers, mental disasters or breakdowns in infrastructure. a healthier campus environment. health professionals, and public health experts The disruption makes entire communities that we urgently need to identify public health vulnerable, especially during public approaches to promote good mental health.” health disasters. WEB EXTRA Similar to past surveys, anxiety (32 per- “We know, based on our recent experi- cent) and depression (27 percent) are the Read the full 2018 College Student Health ence, that there will be more and more most frequently cited mental health condi- Survey report at z.umn.edu/2018CSHS. incidents where necessary drugs or medi- tions among students at the U. M|B cal supplies will be unavailable to those in crisis and, increasingly, the consequences are truly about life and death,” says U to lead $9.7M project to improve hearing restoration CIDRAP director Michael T. Osterholm, Ph.D., M.P.H., who will colead the team The University of Minnesota will lead a research effort to develop a new implantable device with Amy Kircher, Dr.P.H., codirector of and surgical procedure aimed at restoring more natural hearing to people who are deaf or the U’s Strategic Partnerships and severely hard-of-hearing. The work is funded by a five-year, $9.7 million grant from the Research Collaborative. M|B National Institutes of Health BRAIN Initiative. Cochlear implants have long been an effective treatment option for people with hearing loss caused by a lesion or disease of the inner ear or the auditory nerve. Unfortunately, some people aren’t able to benefit from cochlear implants because of anatomical variations in their cochlea that limit the ability to implant the device or sufficiently activate the auditory nerve. The goal of the new grant project is to implant electrodes directly into the auditory nerve, providing access to the hearing pathway and improving activation of the auditory pathway to the brain. Investigators believe this could be helpful for hearing in noisy environments. “We hope that our proposed auditory nerve implant could lead to a new generation of neural technologies and greatly advance novel treatment options in the hearing implant industry,” says Hubert Lim, Ph.D., associate professor in the College of Science and Engineering’s Department of Biomedical Engineering and the Medical School’s Department of Otolaryngology. M|B
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Beyond biology
“AS A HUMAN BEING, I cannot say, ‘No, go back.’ I will see you because I am a community health worker.” This is how Jeanne, a CHW in Rwinkwavu, Rwanda, proudly explained that she would never deny health care to her neighbor.
As one of 45,000 CHWs in Rwanda, Jeanne is on the frontline of the country’s health system. And in this system, the health of your neighbor is a priority.
Jeanne is also one of many instructors in the social medicine course “Beyond the Biological Basis of Disease.” The course is led by SocMed, a nonprofit health-equity education organization based in Minnesota and Uganda. The truly global classroom now has more than 240 alumni from 16 countries, including six medical students from the University of Minnesota.
I took the SocMed course to build my skills in treating systemic health inequities. My experience with medical education before the course largely involved the biological causes of disease; it rarely considered the social struc- tures in which health takes place. Training in social medicine would enable me to dig into inequitable systems and then organize people to respond.
Unlike Jeanne, many forces in the world say, “No, go back,” denying people health care. In the United States, this takes the form of copays and high deductibles. In other countries, these barriers were established by multina- SUBMIT YOUR WORK tional lenders who pressured nations to privatize their public health systems. The Medical Bulletin is seeking com- pelling photos and stories featuring Such large-scale system failures can appear overwhelming. But the U of M Medical School student, alumni, or faculty experiences abroad. Selected response — and the path toward equity — involves the education of tomor- submissions will be published in future row’s health professionals. If education incites action, which is central to issues of the Medical Bulletin. For more information or to submit your social medicine, that means hope for the future. photo or story, email managing editor Nicole Endres at [email protected]. Augie Lindmark enrolled in the Medical School’s FlexMD program to pursue an Oryema Fellowship in Social Medicine with SocMed. He will graduate from the University of Minnesota Medical School this spring and enter a primary care residency at Yale New Haven Hospital.
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Large-scale system failures can appear overwhelming. But the response — and the path toward equity — involves the education LEANNE ZHANG PHOTO: of tomorrow’s health professionals.
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247683_MB Spring2019 PRINT.indd 9 4/10/19 1:02 PM Can we Turn Back HANNA BARCZYK ILLUSTRATION:
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247683_MB Spring2019 PRINT.indd 10 4/8/19 11:36 AM BY EMILY SOHN the clock on aging?
LIVING LONGER CERTAINLY sounds appealing, hofer says. “What we’re aiming to do is work very process unless it simply means more years of dealing with aggressively on developing therapeutics that target the ills and ailments of old age. fundamental aging processes with the hope that
At the University of Minnesota Medical School, they would then slow or prevent or attenuate the aging researchers are working toward a better option: a whole suite of diseases we expect in old age, from
prolonged period of healthy life before the onset of cancer to Alzheimer’s.” the diseases commonly associated with aging. Instead Making 80 the new 60 of a longer lifespan, this lengthened “healthspan” would mean more years to work, travel, and pursue Historically, research efforts to extend life focused an active lifestyle. Dementia, cardiovascular on attacking one aging-related disease at a time, disease, osteoporosis, and other disabling condi- says S. Jay Olshansky, Ph.D., an aging expert at the tions would be delayed — or possibly prevented. University of Illinois, Chicago, but discoveries in A healthier old age is looking increasingly recent years have started to make biological aging seem like less of an inevitability. Instead, experts possible, says Laura Niedernhofer, M.D., Ph.D., by disrupting director of the U’s new Institute on the Biology are increasingly looking to delay the point at which of Aging and Metabolism (iBAM), where she and our bodies begin a rapid decline toward frailty and colleagues are working to develop drugs that slow disease. “We want an intervention that will allow
aging at the cellular level. Called senolytics, these us to take 80 years to become 60,” Olshansky says. longer drugs would offer huge benefits across society, Paul Robbins, Ph.D., iBAM’s associate director, Niedernhofer says. More than 90 percent of people has seen his career mirror the field’s overall shift over 65 have one chronic disease, she says, and in thinking — from dealing with aging-related 75 percent have two or more chronic diseases; diseases after the fact to slowing their progression vibrant 10,000 people in the U.S. turn 65 every day. before they begin. His early interest was in gene “That’s a lot of sick people and it just robs therapy — looking for ways to correct genetic quality of life, not only for them but for their defects or transfer genes to treat diseases like and family members who are caretakers,” Niedern- rheumatoid arthritis and diabetes. Then, about healthy U scientists are discovering drugs that may keep people HANNA BARCZYK ILLUSTRATION:
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247683_MB Spring2019 PRINT.indd 11 4/8/19 11:36 AM Experts are increasingly looking to delay the point at which our bodies
15 years ago, he started to find evidence that similar DNA-repair enzyme. Without the ability to fix their molecular processes drove the development of all DNA, the rodents aged six times more quickly than sorts of aging-related diseases. normal. In people, she found, related mutations cause He switched gears to focus on those molecular a rare disease of accelerated aging. processes, which can be tinkered with to cause either Now, Niedernhofer and Robbins had both a feasible age-related diseases or extreme longevity in a variety idea and an animal model for investigating the biologi- of animal models, including fruit flies, mice, and cal processes that drive aging. Lured by iBAM’s worms. “There were certain types of mutations that commitment to aging research, the duo, both leaders made their lives shorter,” he says, “and certain similar in their field, moved from the Scripps Research mutations that allowed them to live longer.” Those Institute in Jupiter, Florida, to the U of M Medical mutations also have parallels in human centenar- School, where they are professors in the Department ians, suggesting that senolytic drugs could target the of Biochemistry, Molecular Biology, and Biophysics. same processes in people, permitting them to live Their recruitment resulted from a $30 million longer, healthy lives. initiative launched by former Gov. Mark Dayton and Over the same period, Niedernhofer’s research the state Legislature in 2014–15 that created four produced a striking discovery that made an age- Medical Discovery Teams in the Medical School, slowing approach seem even more feasible. To better including iBAM, to improve patient and population understand the health consequences of DNA damage, health, lower medical costs across the state, and fortify she knocked out a gene in mice that codes for a the Medical School’s preeminence.
Laura Niedernhofer, M.D., Ph.D., and Paul Robbins, Ph.D., who lead the U’s new Institute on the Biology WILLETTE BRADY PHOTO: of Aging and Metabolism, believe healthier old age is increasingly possible.
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247683_MB Spring2019 PRINT.indd 12 4/8/19 11:36 AM NEW CARE MODELS Experts are increasingly looking to delay the point at which our bodies begin a rapid decline toward frailty and disease. FOR OLDER PATIENTS
THE MEDICAL SCHOOL is expanding its commitment to educating and training today’s physicians to care for tomor- Targeting troublesome senescent cells row’s geriatric patients — those over age 60. Jakub Tolar, M.D., Ph.D., Medical School dean and vice At iBAM, one major focus targets senescent cells, president for clinical affairs, says the revitalized relationship which form in our bodies in response to stress. between the University and Fairview Health Services pro- Senescent cells do the important work of suppressing vides a prime opportunity to create an integrated system tumor formation by preventing damaged DNA from of care for seniors, whose numbers will double by 2030. replicating, but senescent cells also accumulate with “Throughout the University, we have extensive knowl- age, as our bodies get worse at getting rid of them. edge of the biology, psychology, and other aspects of While they hang around, senescent cells release aging — and we educate 70 percent of the state’s primary molecules that induce a state of chronic inflammation, care physicians,” says Tolar. “Our family medicine leaders which has been linked to many of the health conse- are collaborating with experts across many fields to quences of aging, like slower recovery from surgeries. develop state-of-the-art geriatrics care training programs For a 2015 study, Niedernhofer and Robbins, along and to deliver coordinated care for seniors through our with colleagues at the Mayo Clinic, developed the expanded network of primary care sites.” first drug to kill senescent cells. They gave mice an A wider network is just part of the plan, says James existing cancer medication called dasatinib, along Pacala, M.D., a geriatrician and head of the Department with a common plant pigment called quercetin, and of Family Medicine and Community Health. “We need a found that the old rodents maintained a healthy different approach to adapt to the varying needs of geriat- gait, stronger heart function, and the ability to ric patients, from the 90-year-old super-athlete to the exercise longer. A single dose was enough to slow 60-something patient with 18 medical conditions and the aging process. 25 drugs.” Since then, the scientists have pushed the possibili- Tolar and Pacala envision drawing on faculty experts in aging from the University’s schools of medicine, public ties even further. In one study, published in 2018, health, and nursing; pharmacology; physical therapy and iBAM researchers and colleagues at Mayo found that rehab; dentistry; as well as social work and other programs. transplanted senescent cells caused physical decline This comprehensive effort, says Pacala, will serve as an in young mice and reduced survival in older mice. engine for training and research that will benefit older PHOTO: BRADY WILLETTE BRADY PHOTO: But the effect was reversible: a senolytic cocktail of patients, their families, and caregivers. dasatinib and quercetin lowered the load of senescent cells and the inflammatory molecules they produce. $1M BOOST FROM OTTO BREMER TRUST The drug also improved physical abilities, such as Though still in the planning phase, the initiative has drawn walking speed and muscle strength. And it length- the support of the Otto Bremer Trust, which recently ened the rodents’ lifespans by 36 percent. In another awarded the University a $1 million grant to develop inte- 2018 study, the group reported similarly encouraging grated education for all types of students — not just future findings with another plant compound, called fisetin, geriatricians — who will deliver care to older patients. even if the medications were given to the mice later The Medical School plans to use the Otto Bremer sup- in life — the equivalent, Niedernhofer says, of treating port to provide geriatrics training for primary care clinics a 75-year-old human. and to develop a telemedicine program that reaches older continued adults in their own communities, says Tolar. “I’m confident we can transform care for this growing population.”
By Mary Koppel
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247683_MB Spring2019 PRINT.indd 13 4/8/19 11:36 AM If we don’t do something, we’re in a world of trouble. There are not enough
Although mice are not people, evidence is Although hype has been building, it is too beds adding up to support the powerful potential of soon to recommend that people start self- new medications to defer aging, Niedernhofer medicating to fight aging, she adds. Plenty of says. She and Robbins continue to work with details remain undetermined about what form nursing in collaborators at Mayo to develop new drugs that the medication will take, how often people will interfere with what Robbins thinks are just a get it, or who will be the target patient popula- handful of pathways involved in aging. They are tion. New medications will also have to be also working to fill in more details about the tested exhaustively for safety, but startup fundamental processes that drive aging in order companies are increasingly interested in to collect new insights that will inform drug investing in senolytic drugs, says Robbins. One homes development. One hope is to create medications of the first groups to benefit might be cancer that would target specific locations, like the patients, who tend to accumulate extra senes- brain or immune system. cent cells and experience accelerated aging from harsh treatments. Initially, the drugs will also to TAMING the aging process
likely be geared toward people who already are accommodate The first clinical trial of a different type of drug showing signs of unhealthy aging, having two with anti-aging potential is scheduled to begin or more age-related diseases. this year. Called TAME and developed with Given the cutting-edge research happening at guidance from the iBAM directors, the trial is iBAM, the next major breakthrough in senolyt- examining whether Metformin, a diabetes drug ics is likely to happen in Minnesota, Olshansky that has shown promise for delaying the onset says. The availability of drugs that slow aging, of multiple age-related diseases, might be able to he adds, is a matter of when, not if. delay the development of cancer, heart disease, “When it does happen — when some research and cognitive decline in all older adults, not just team somewhere across the globe develops a all people with diabetes. The University of Min- therapeutic intervention to modulate aging — of nesota is one of 14 sites where the TAME trial it will probably become the most important
will take place. Metformin is not a senolytic, as medical discovery in this century because of the it doesn’t target senescent cells, but it could get the breadth of its impact on humanity,” he says. at the heart of aging. And, depending on its “It will make a cure for cancer seem like a baby aging results, the trial could transform old age — and minor development.” M|B soon. “The first drug for aging could be here in the next five years,” Robbins says. Emily Sohn is a freelance journalist in Minneapolis whose Niedernhofer sees the research as a necessity, stories have appeared on NPR and in the Washington Post, Nature, and many other publications. not a luxury. “If we don’t do something,” she says, “we’re in a world of trouble because there
are literally not enough beds in nursing homes boomers. or independent living facilities to accommodate all of the aging baby boomers.”
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247683_MB Spring2019 PRINT.indd 14 4/8/19 11:36 AM Points of pride Nationwide, schools still struggle to draw Native Americans and Alaska Natives into medicine; here’s what’s working at our Medical School’s Duluth campus
BY JUSTIN HARRIS
Mary Owen, M.D., directs the Medical School, Duluth campus’ Center of American Indian and Minority Health, a resource and community hub for Native students.
MEDICAL BULLETIN SPRING 2019 15 DEREK MONTGOMERY PHOTO:
247683_MB Spring2019 PRINT.indd 15 4/8/19 11:36 AM s a kid, Fredrick Blaisdell saw first- national leader in addressing health challenges hand some of the all-too-common in Native communities. health challenges facing American The Medical School’s history of success was Indian and Alaska Native people highlighted by a report released in October acrossA the country: insufficient access to health 2018 — written by the Association of American care, a dearth of Native physicians to provide Medical Colleges (AAMC) and the Association of that care, and an overall lack of resources American Indian Physicians (AAIP) — that sheds available to the community. light on the myriad health concerns plaguing “I saw it as a patient and with my family,” American Indian and Alaska Native communi- says Blaisdell, a member of the Oneida Nation ties and explores the responsibility that medical of the Thames who grew up in an urban Native schools have to combat these conditions. American community near Detroit, Michigan. “Part of our land-grant mission is to provide “We often struggled to get the services care for anyone who lives in Minnesota, and we needed.” we recognize that some of our greatest health disparities exist within our Native communi- ties,” says Paula Termuhlen, M.D., regional I wanted to go to a school that included campus dean of the Medical School in Duluth. “We want to understand the challenges these American Indian health as a main focus. communities have and how we can use our resources to help support them.” When I came to visit campus for my interview, Understanding the problems right away it felt like home. The AAMC/AAIP report outlines the uniquely daunting set of circumstances that contribute – Fredrick Blaisdell, Medical School, Duluth campus student to poor health in Native communities. Histori- cal trauma and continued marginalization in That experience was pivotal in his decision American society have made it difficult for to pursue medicine as a career, with the goal Native people to access high-quality care and of working as a doctor in a Native community. have contributed to some of the worst health When it came time for Blaisdell to apply to outcomes in the country. medical school, one place stood above the rest: Native people experience higher rates of the University of Minnesota Medical School, many chronic and preventable diseases than Duluth campus. other Americans and have a life expectancy “I wanted to go to a school that included that is nearly six years shorter. According to American Indian health as a main focus,” says the report, about 25 percent of deaths in Native Blaisdell, a first-year medical student at the people occur before the age of 45, compared Duluth campus and one of six Native American with 15 percent for African Americans and students in his class. “When I came to visit only 7 percent for whites. campus for my interview, right away it felt Compounding those factors, the report like home.” argues, is a lack of Native physicians and Since its inception in 1972, the Medical medical professionals serving in these commu- School’s Duluth campus has made Native nities. Fewer than l percent of doctors working American health a fundamental part of its in the United States in 2016 identified as mission. Over the course of four decades, the American Indian or Alaska Native, and the Medical School has trained more than 170 number of Native students applying to medical Native American physicians — the second- school across the country remains relatively highest number in the country — and become a stagnant at about 200 a year, despite efforts to improve these numbers.
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Mary Owen, ’00 M.D., director of the Medical School, Duluth campus’ Center of American Indian and Minority Health (CAIMH) and practicing physician for the Leech Lake Band of Ojibwe, acknowledges that the confluence of issues affecting Native health can be over- whelming. But she says the Medical School is in a unique position to help. “We have complex problems,” says Owen, a member of the Tlingit Nation. “But we also have solutions.” Training the next generation The most obvious solution is an emphasis on recruiting and training Native physicians, a priority that dates back to Duluth’s first class of medical students. In that class of 24, two were Native students. All told, the Medical School has graduated 177 Native physicians. “The school has been committed to support- ing Native American students for almost 50 years,” says Anna Wirta-Kosobuski, Ph.D., an assistant professor in the Department of Biomedical Sciences on the Medical School’s Duluth campus, who contributed to the AAMC/ AAIP report and is a member of the Bois Forte Band of Ojibwe. “The longevity and level of com- mitment set us apart.” Owen says the supportive community on campus is a significant reason for the school’s sustained success. CAIMH engages students in Native health issues through programs like the Indian Health Pathway, which supports middle school, high school, and undergraduate stu- dents in their pursuit of health-related careers. Another initiative, Native Americans into Medicine, is a six-week summer program for premedical students to collaborate on specific PHOTO: COURTESY OF THE CENTER OF AMERICAN INDIAN AND MINORITY HEALTH OF THE CENTER AMERICAN INDIAN AND MINORITY COURTESY PHOTO: research projects related to Native health.
TOP Fredrick Blaisdell, a first-year medical student at the Duluth campus, is a member of the Oneida Nation of the Thames.
BOTTOM The Native Americans into Medicine program gives undergraduate students interested in medicine hands-on research experience.
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AMERICAN INDIANS 4,099 43 AND ALASKA NATIVES Number of Native physicians Percent of medical schools practicing in the U.S. — that had no AI-AN students IN MEDICINE less than 1 percent of the enrolled in 2016–17 physician workforce
Through such programs, students build Owen says, is that the more non-Native students WEB EXTRA relationships with their peers, faculty and staff, know about Native communities — and the See photos of students in and the broader Native community in Minne- health issues they face — the more motivated the Native Americans into sota, Owen says. they’ll be to serve these populations. Medicine program, or read “We’re building a community and we’re Beyond medical school the full report on health letting everyone that we come in contact with concerns plaguing Ameri- know about Native health issues and concerns, Medical School leaders agree that the school’s can Indian and Alaska Native communities, and our culture,” she says. responsibility to Native health goes beyond Native communities, Training more Native physicians is a worth- training the next generation of physicians, at z.umn.edu/CAIMH. while pursuit, Owen says, but it won’t overcome because the disparities in these communities the health disparities in Native communities. go beyond health. Federal Indian Health Service clinics across One area that the Medical School has targeted the country — where more than 2 million Native in recent years is early education. Community- people receive health care — have a 25 percent based science initiatives led by Wirta have vacancy rate for physician openings, a number brought fun and engaging science activities to that Owen says cannot be filled solely by elementary school children in Native communi- Native physicians. ties in Minnesota. Three years ago, and with that challenge in “The thought behind working with the young mind, the Medical School introduced a required children is that by the time they reach even curriculum for all students that covers Native middle school, it can be too late to effectively history, culture, and identity. The thinking, address student needs and provide interventions that promote educational success,” Wirta says. “By third grade, many Native American children have not made it to the benchmarks where they need to be in order to move on.” Anna Wirta-Kosobuski, Ph.D., leads The statistics back up her assertion: In community-based science programs Minnesota, the high school graduation rate that encourage elementary school among Native American students stands at children in Native communities to only 50 percent. PHOTO: DEREK MONTGOMERY PHOTO: engage in science at an early age. “That’s what pushed me toward working with the young children. They have a natural curiosity, and, ideally, we can reach them before they start to lose interest in the excitement of learning,” Wirta says. “The goal is that they’ll graduate from high school, and move on to postsecondary education. The long-range goal is that they go into some sort of science career, which would be a huge bonus.” Termuhlen calls the idea of addressing education shortcomings at the earliest opportu- nity an “aha moment” for the Medical School.
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43 2 2 46 13 Percent of medical schools Nationwide ranking in Number of AI-AN students Years Native Americans into Percent of Duluth campus Source: Reshaping the Journey that had no AI-AN students number of AI-AN graduates in the Duluth campus’ first Medicine, a summer enrich- faculty who are AI-AN (October 2018) from the Association enrolled in 2016–17 (177) enrolled class of 24 students, ment program at the Duluth individuals of American Medical Colleges in 1972 campus for Native American and the Association of American and Alaska Native premedical Indian Physicians students, has been held
“We realized we have to take a step even further back and start to engage,” she says. “If we were to follow those students into the future, how many of them get through high school? Can we start to budge that high school gradua- tion rate? We know educational successes will translate into economic successes, and that supports improvement in health outcomes.” And, as Owen notes, if more Native students are going to college, how many might pursue
careers in health-related fields? PH.D. OF ANNA WIRTA-KOSOBUSKI, COURTESY PHOTO: “We need more Native pharmacists, more Native nurses, more Native public health specialists, more Native dentists,” she says. “That’s why these community-based science activities are so important.” ‘Nobody gets here on their own’ For all of the innovative programs the Medical School has developed to address Native health issues, it’s how the Native community has “The strong community on campus and that Students at Nett Lake Elemen- become an integral part of Duluth campus’ DNA cultural connection reminded you why you tary School build DNA models that makes Owen most proud. It’s a community were meant to do this, and it motivates you to using candy as part of a com- that embodies Native values, she says. munity education program. keep going,” recalls Running Hawk, who “We want this to be like a Native community, shadowed Native physicians and volunteered in which is not built on individualism, but just the Native communities while in medical school. opposite,” she says. “It’s built on supporting one WEB EXTRA “Having the mentorship from Native physi- another, believing that we’re all connected, and cians, it also gives you the heart to want to be Watch Wirta lead Nett that we all help one another. Nobody gets here that mentor to others.” Lake Elementary School on their own.” And that’s exactly what Running Hawk has kids through hands-on That full-circle ethos is evident in efforts like done. She’s now a community preceptor for the science experiences at Wirta’s early education outreach initiative. It’s Medical School’s Rural Family Medicine, Native z.umn.edu/CAIMH. also reflected in mentorship opportunities that American and Minority Health Scholars Program. offer medical students a chance to shadow and “We have this idea that you are where you are work alongside practicing Native physicians in because somebody reached back and helped you,” those communities. Running Hawk says. “And now it’s my responsi- Lacey Running Hawk, ’13 M.D., a member of bility to do that for the next generation.” M|B the Standing Rock Lakota and a family medi- cine physician for the Mille Lacs Band of Ojibwe, Justin Harris is an editor-writer with the University of says those experiences in medical school Minnesota Foundation. continue to shape who she is as a doctor today.
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247683_MB Spring2019 PRINT.indd 19 4/10/19 1:02 PM Going cell-to-cell with ovarian cancer Masonic Cancer Center researchers evaluate a unique immunotherapy designed to keep this wily disease from coming back
BY BARBARA KNOX Melissa Geller, M.D., M.S., was still a new doctor Cancer Society. The majority have a recurrence completing her fellowship at the University of within two years, and, despite the best efforts of Minnesota in the early 2000s when she resolved doctors like Geller, five-year survival rates for to spend the rest of her career helping people ovarian cancer are less than 50 percent. who face the grimmest of cancer diagnoses. While current treatments for ovarian “Having to tell a patient with ovarian cancer cancer — surgery to remove the tumor followed that there is no cure for her disease is incredibly by six months of chemotherapy — attack the difficult,” says Geller, now associate professor disease from the outside, the cell therapy trials and division director of Gynecologic Oncology underway now take the fight to the cancer’s in the Medical School’s Department of Obstet- front lines: inside the body, where the battle is rics, Gynecology, and Women’s Health. “I knew being waged on a cellular level. then that, someday, I wanted to be able to say to Immunotherapy treatments — including cell these women, ‘You will never have a recurrence therapies — are designed to harness the power of of this cancer.’” the body’s immune system to kill cancer cells And today she’s optimistic about a form of by either delivering new cells to the fight or immunotherapy originally developed by her revving up the ones already there. Both of Masonic Cancer Center, University of Minne- Geller’s trials hinge on natural killer (NK) cells. sota colleague and mentor Jeffrey Miller, M.D., In a healthy body, NK cells rally to the site of a professor of medicine in the Medical School. infection or disease and call other cells to come Through a partnership with the biotechnology to that location and help beat back the infection. company Nant, Geller and her team are now But cancer cells are wily and elusive. And treating women who have recurrent ovarian researchers now know that women with cancer in two early-phase clinical trials. ovarian cancer have fewer NK cells in the perito- While Miller has used this type of immuno- neal area — and the ones they do have function therapy to treat people who have blood-related poorly, which allows cancer cells to flourish. diseases, Geller’s studies are the first to explore In the first trial, Geller is administering a whether it can be effective against solid tumors. cell therapy called FATE-NK100, developed by investigators at the University in collaboration Promise of cell therapy with Fate Therapeutics, directly into each The stakes are high. More than 22,500 women patient’s peritoneal cavity through a port in the are diagnosed with ovarian cancer every year abdomen. The treatment is derived from the in the United States, according to the American blood of a related donor. Six patients have been
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247683_MB Spring2019 PRINT.indd 21 4/8/19 11:36 AM PHOTO: BRADY WILLETTE BRADY PHOTO: EXPLORING THE CMV– OVARIAN CANCER LINK CYTOMEGALOVIRUS, or CMV, infects more than half of all adults by the time they turn 40. For most people with healthy immune systems, the virus causes no signs or symptoms. But for women who have ovarian cancer, the virus has unknown — and potentially important — effects on their treatment and quality of life. Research- ers suspect that CMV reactivation may be an unrecognized complicating fac- tor in the treatment of ovarian cancer Melissa Geller, M.D., leads two clinical trials using natural killer cell–based immunotherapy to knock out that could affect both recurrent ovarian cancer. immune function and outcomes. treated so far, and, Geller reports, she’s bringing them to patients, but also for Now, with support finding that those donor NK cells are still changing and adapting the treatments from two Department at work more than a month later. quickly as researchers make new discover- of Defense grants, “The longer those NK cells stick around,” ies in the lab. researchers at the Geller explains, “the more — hopefully — The next big push University of Minne- we will see the disease stabilize, so we can sota are investigating keep the patient off chemotherapy.” While immunotherapy has fundamentally Rachel Vogel, Ph.D. how CMV reactivation That trial, which is focused on establish- changed the landscape of cancer treatment, affects women who ing optimal dosing for the FATE-NK100 it’s massively expensive to develop person- have ovarian cancer during the course treatment, will go on for another year. alized cell therapies derived from donors of their disease. In the second trial, Geller uses the drug for every patient. So researchers have been Rachel Vogel, Ph.D., assistant pro- developed by Miller’s team in its partnership busy in recent years trying to create a fessor in the Medical School’s Depart- with Nant. Geller describes it as a “souped- one-size-fits-all treatment that is both ment of Obstetrics, Gynecology, and effective and affordable. Women’s Health and researcher at the up agonist that sends in a combination of NK cells and T cells to attack the cancer According to Miller, who is director Masonic Cancer Center, received a of the Masonic Cancer Center’s Cancer $1.1 million grant to study how CMV cells where they grow.” (T cells are also key Experimental Therapeutics Initiative, that’s affects patients’ symptoms during players in a healthy immune system.) Again, the next step — and it’s already well under- ovarian cancer treatment. She’ll be the treatment is delivered directly into the way at the University. working with Masonic Cancer Center abdomen — a first for this drug — on a “Working with Fate, our next big push is colleagues Melissa Geller, M.D., and four-weeks-on/four-weeks-off schedule. to develop an off-the-shelf NK cell therapy Heather Nelson, Ph.D., on the study. “Our goal is to prevent cancer recurrence The same team, this time led by and, if it works, that ultimately this will product,” he says. “We know how to make Nelson, was also awarded a $385,000 become a treatment that women could pluripotent stem cells (adult cells that are pilot grant to study the CMV–ovarian give themselves at home,” she says. genetically reprogrammed) into NK cells, cancer interaction over an extended With only four women in the trial so now we have the opportunity to make period of time. so far, Geller continues to recruit addi- a big batch of hundreds of doses.” “By understanding how the virus tional patients. Using that approach, Miller explains, is impacting symptoms and treat- Geller credits the U’s unique blend doctors could simply go to the freezer, ment, we can design interventions of translational research laboratories, a remove a dose, and administer it to a to improve outcomes and quality of pharmaceutical-grade manufacturing patient: faster, cheaper, and, ideally, every life,” Nelson says. facility, and dedicated oncology clinics for bit as effective as those painstakingly not just developing the treatments and manufactured personalized treatments. That’s what Miller aims to confirm when
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the disease from the outside, trials underway now STREBLE SCOTT PHOTO: take the fight to the front lines: inside the body, where the battle is being waged on a cellular level.
he treats his first patient in a new trial that If all goes well in the upcoming trial, he expects to start later this year. Miller says, best-case scenario, they could Meanwhile in the lab, Miller’s next major have a commercial cell therapy ready to be project is creating a new type of NK cell used in the clinic in five years. that is hyper-focused on ovarian cancer. “Five years is quick,” he cautions, “but Will NK cells designed to have extra this field is moving quickly.” Jeffrey Miller, M.D., has found success in employing specificity be even more effective in their For the ovarian cancer patients that natural killer cells against blood cancers and is hoping the success translates to solid tumors like search-and-destroy mission? That’s what Geller sees in clinic every day, the prospect ovarian cancer as well. Miller and his team aim to find out. of an effective cell therapy is a ray of hope. After more than two decades in the field “I’m so grateful for the mentorship I’ve and a lot of pioneering research behind gotten from Jeff [Miller] and all the work he him, Miller believes this work can spur a and his team have done to develop this cell WEB EXTRA revolution in cancer treatment. therapy,” says Geller. “And I’m especially Masonic Cancer Center researchers are devel- “One thing I’ve seen in my many years grateful that now women with ovarian oping a blood test to screen for ovarian cancer. doing this work is that pharmaceutical cancer can benefit, too.” M|B Learn more at z.umn.edu/ovariancancertest. companies only invest with a goal of Barbara Knox is a freelance writer and editor and commercializing treatments if they think a frequent contributor to the Medical Bulletin. it’ll be a game-changer,” he says. “And they’re investing.”
BUILDING A BETTER APP HOW DO YOU GET women who’ve been diagnosed with To determine whether the app was effective in convincing
ovarian cancer to undergo genetic testing? It’s a surpris- women to seek genetic testing, Geller gave one group of GOOD ingly hard sell, says University of Minnesota Health women an informational pamphlet, while the other group had gynecologic oncologist Melissa Geller, M.D. access to the app. Sometimes women are concerned that their insur- “Women who used the app learned more about hereditary ance won’t pay for genetic counseling, while others are ovarian cancer and were more apt to talk with family members SOFTWARE FORIMAGE: fearful of what they might discover. What if they find out about it,” Geller says. “It’s a potentially very powerful tool.” that they carry gene mutations like BRCA1 or BRCA2, It’s also more important than ever to get women tested. “We which increase risk of breast and ovarian cancer? And, now have drugs that have been shown to improve survival in if they do carry a mutation, they fear they may have women who are BRCA-positive,” she says, “so testing is critical.” passed it along to their children. Sharing that news While the first version of mAGIC performed well, Geller now with your kids is tough. wants to take it to the next level. With the help of philan- Geller decided to tackle the information barrier with thropy, she plans to update it to keep getting information out an app. With funding from the Department of Defense, to at-risk women and their family members. she developed mAGIC (mobile application for genetics in Find out how your gift can help to develop the next-generation cancer), a seven-day educational app designed for mAGIC app by contacting Lacy Moser of the University of Minne- women who have ovarian cancer who haven’t gone sota Foundation at 612-625-6495 or [email protected]. through genetic counseling.
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247683_MB Spring2019 PRINT.indd 23 4/8/19 11:36 AM WOYCHICK GETTING IT RIGHT DAN ILLUSTRATION: Diagnosing illness is one of the most impor- small amount of intuition that defies easy How doctors tant things doctors do. Yet they get it wrong explanation. in training can a small but significant part of the time. “Until recently, we have not understood “We are not nearly as good at diagnosis terribly well the processes we use to make learn to avoid as we thought we were,” says Andrew Olson, diagnoses,” says Olson. “When we don’t M.D., assistant professor of medicine and understand the process very well, how do we making the pediatrics in the University of Minnesota teach it?” wrong diagnosis Medical School. “We produce people who As a result, diagnosis has been taught more are right 85 to 90 percent of the time in the implicitly than explicitly. Young doctors learn hospital and 95 percent of the time in outpa- to take medical histories and then follow BY GREG BREINING tient settings. That’s not good enough.” more experienced mentors who impart — To improve doctors’ skills, Olson has been clearly or not — their own diagnostic meth- spearheading efforts in the Medical School’s ods. That sort of learning leads to uneven undergraduate and graduate programs to results. And, research shows, reliance on teach diagnosis more systematically and intuition and mental shortcuts at the wrong comprehensively. times leads to errors. “In my opinion, the most promising strat- COGNITIVE BIAS egy is to improve education,” he says. “If I teach a student who is then going to practice Medicine has treated knowledge as the for 40 years and see thousands and thousands basis of good diagnosis. But, as Olson and of patients, the impact potentially is huge.” colleagues recently noted in the journal Though fundamental, diagnosis is one of Diagnosis, “knowledge is necessary but the most complex things a doctor does; it’s not alone sufficient.” based on a combination of subjective informa- “The reasons I err aren’t necessarily that tion, objective tests, rational thought, and no I didn’t know a fact,” says Olson. “If you look at what gets missed in the hospital, it’s things
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like sepsis, strokes, heart attacks. What gets a good diagnostician — keeping an eye on missed in outpatients? Cancer, most com- what your intuitive system is doing.” monly. Why is that? We know a lot about all Writing in the New England Journal of those things. It’s not a knowledge problem Medicine, Croskerry described a patient who alone. It’s that I put the pieces together the came to the hospital with stab wounds to his wrong way.” arm, back, and chest. After ascertaining that That happens because doctors rely on the wound to his back did not penetrate the intuition when circumstances require more chest cavity, doctors patched him up and deliberation, explains Pat Croskerry, M.D., sent him home. Five days later, the man went who leads the Critical Thinking Program in to another hospital in the area complaining the Division of Medical Education at Dalhou- of vomiting and blurred vision. A CT scan sie University in Halifax, Nova Scotia. revealed a knife wound several inches into “In an emergency setting, I can see one his brain. problem after another, and I can function at “Anchoring bias” led the resident to focus on an almost intuitive level and say this almost the most obvious injuries, to the exclusion of always turns out to be that, and that’s how the head wound. “Even though you think you I’m going to treat it,” says Croskerry, a may be being vigilant and careful, you can still coauthor of the Diagnosis paper. “A patient get caught on these biases,” says Croskerry. may come in who is constipated. Constipation Scientists have written about biases for is pretty straightforward in 99 percent of 40 years, but medicine has largely overlooked cases.” A laxative solves the problem. But the research because it is so intangible (see infrequently, constipation may be caused by sidebar, page 27). a growing tumor or neurological problem. “It’s something that goes on between the Doctors must “be alert to the possibility physician’s ears,” says Croskerry. “Anybody that what you’re seeing may not be routine,” observing my behavior from the outside says Croskerry. “That’s the real trick in being
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247683_MB Spring2019 PRINT.indd 25 4/8/19 11:36 AM The human doesn’t really know what my brain was going inquiry, says Olson. “I think a lot of the reason through when I made that decision. But cogni- we label stuff early on is because we are uncom- brain is wired tive scientists do. And medicine really hasn’t fortable saying, ‘I don’t know, but I’ll be with embraced cognitive science and asked questions you.’ That’s probably one of the most important to believe we’re about how we think.” things that we can do as clinicians.” Teamwork can improve diagnosis as well. BETTER STRATEGIES correct. Being Medical teams, which are often hierarchical, Olson agrees that cognitive shortcuts lead to can learn from aviation. Air crews, from pilots right and errors, but he questions whether simple aware- to copilots to flight attendants, speak up if ness will lead to dramatic improvements. something doesn’t seem right. being wrong “Maybe that is the problem, but addressing it might not be the solution,” he says. “I think WOVEN INTO THE CURRICULUM feel exactly what we’re all working on now is what strate- A more systematic approach to teaching gies may be helpful to avoid some of those diagnosis has been creeping into medical school the same until cognitive errors? We all know the worst curricula as practitioners and faculty realize strategy in the whole world is to ‘try harder.’” the shortcomings of learning diagnosis strictly someone tells What might work? by doing. Developing skills in “reflective practice” is “The notion even that there was a science you you’re one possible strategy, says Olson. Making a grid around clinical diagnosis is a relatively new of possible diagnoses — “What’s for it? What’s concept,” says Robert Englander, M.D., associate wrong. against it?” — can force a physician to reason dean for undergraduate medical education. “It’s more deliberately. moving from an implicit approach to an explicit – Andrew Olson, M.D. Another is feedback. “The way training is approach around clinical reasoning. Only in the now, a student or resident admits a patient at last 10 to 15 years has there been an exploding night, they go home, they don’t find out what focus on patient safety and quality. The atten- happened to that patient. So they think they’re tion to clinical diagnostic reasoning has sprung right. The human brain is wired to believe out of that movement.” we’re correct. Being right and being wrong To help students develop these skills, the feel exactly the same until someone tells you Medical School weaves in lessons in diagnostic you’re wrong,” says Olson. The Medical School thinking right from the start and throughout participated in a recent study with six institu- the undergraduate and graduate experiences, tions to bring feedback into training programs. says Englander. “We found that the diagnosis changed about A course called Foundations in Clinical 40 percent of the time — a lot.” Thinking spans the first two years of medical Doctors should also be willing to admit school and allows students to work with they don’t know. Pressure to diagnose leads to clinical problems and generate differential “premature closure” and can stymie further diagnoses. At the Medical School’s Duluth
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247683_MB Spring2019 PRINT.indd 26 4/8/19 11:36 AM campus, a problem-based learning thread Olson is particularly proud of the pediatrics WHAT IS BIAS? during the first two years helps students residency program, which pairs resident doctors think about diagnosis. with role-playing patients in ambiguous Bias influences how and why we There’s also a greater emphasis on team- situations. Residents explain the diagnostic make decisions—and it’s no differ- work, Englander says. Students are engaged process to patients and discuss why a diagnosis ent for doctors. According to a in collaboration with students in nursing, may have to wait. Additionally, faculty discuss report by Pat Croskerry, M.D., in pharmacy, dentistry, and public health. errors they have made in diagnosis, “which is Academic Medicine, common cogni- In Olson’s Advanced Physical Diagnosis really a powerful thing to hear,” he says. tive biases that affect physicians’ diagnoses include: course, fourth-year students study research To minimize such errors, the Medical School literature to evaluate aspects of physical exami- will continue to hone its curriculum aimed Availability bias, which occurs nation that are most useful in making diagno- at strengthening diagnostic skills, develop when recent similar examples ses. Erica Levine, M.D., an internal medicine assessment tools to gauge students’ abilities, (immediately available in the resident, says the course developed her physical and conduct research to determine how well physician’s memory) unduly examination skills and ability to evaluate students are learning. influence a decision about a evidence-based medicine. “There is no one answer and there are no current patient’s diagnosis. “We definitely looked a lot at uncovering easy answers,” says Olson. “If there was an easy Gambler’s fallacy, which is the some myths the medical community holds answer, we would have found it already.” M|B opposite of availability bias and true,” says Levine. “We focused a lot on the occurs when a physician doubts Greg Breining is a journalist and author based in data behind different findings.” the current patient’s diagnosis St. Paul, Minnesota. “I think the main takeaway is to think based on similar diagnoses of critically, because that separates doctors from other patients, i.e., gambles that computers,” adds Gretchen Colbenson, M.D., the trend will not continue. who also took the class. “One of my biggest Confirmation bias, which occurs takeaways is that diagnoses are much grayer when a physician forms an early than anyone would tend to believe before any opinion about a patient’s diag- medical training.” nosis and consequently looks The Medical School is looking for better tests for and favors evidence that to gauge how well students and residents are confirms that diagnosis. learning. Multiple-choice exams are “a pretty Anchoring bias, which occurs bad indicator of diagnostic ability,” Olson says. when a physician locks on to “We need to move to something called a particular symptoms and signs workplace-based assessment, which is our in a patient’s initial presentation ability to actually assess a learner’s ability to and fails to adjust that initial do something in a real-world environment with impression as new data real-world patients. A lot of that is focused on become available. the process they use.”
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247683_MB Spring2019 PRINT.indd 27 4/8/19 11:36 AM Alumni Spotlight | Nathan Chomilo, M.D.
A storybook solution
Alumnus promotes health equity by making books WILLETTE BRADY PHOTO: a standard feature of pediatric care
ONCE UPON A TIME, there was a bow-tie- THE POWER OF clad doctor who believed deeply in the power EARLY READING of books to give babies, toddlers, and pre- An alumnus of the University schoolers their best chance in life. That of Minnesota Medical School doctor’s devotion to early childhood literacy (Class of ’09), Chomilo was steadily grew, and soon led him to advocate appointed to the Governor’s for equity and justice for all. Early Learning Council in 2016, His snappy wardrobe — the colorful bow is active in the Minnesota ties “are part of my look, and they’re also clin- chapter of the American ically better than neckties” (studies show that Academy of Pediatrics (includ- neckties harbor germs) — and his apparently ing serving as an AAP Early boundless energy make Nathan Chomilo, Childhood Champion), and is M.D., seem a bit like a storybook character cofounder and vice president himself. The Park Nicollet pediatrician and of Minnesota Doctors for internal medicine hospitalist serves as medi- Health Equity. Those activities cal director for Reach Out and Read (ROR) reflect his keen interest in Minnesota, which incorporates books and social determinants of reading into pediatric care, and is a go-to health — the conditions into source for media on the vital importance of which people are born, grow, early childhood literacy. work, and age, and which largely account for health inequities. Reading, he says, is a proven way to influence the trajectory of a child’s life. The program capitalizes on a critical window THE READ-ALOUD HABIT Chomilo’s involvement with ROR Minnesota of brain development — during a child’s first began in 2009 when he was in the second three years — and the unique physician-patient Today, one in three children in Minnesota week of his internship and ROR’s then-medical relationship to give kids a foundation for suc- between 6 months and 5 years attends a director, Laurel Wills, M.D., came to speak at cess. Chomilo was captivated; after the lecture, clinic that participates in Reach Out and a lunchtime lecture he attended. he asked how he could get involved. Today, he Read (ROR). Two-thirds of those children “She talked about this simple intervention is the state chapter’s medical director. live in the Twin Cities metro area. “My done during pediatric well-child checks, Evidence of the program’s impact continues goal, and ROR’s goal, is to make this the where the doctor talks about the importance to mount: families served by ROR are 2.5 times standard of care for pediatrics in all of of books and gives a book that’s appropriate more likely to enjoy reading together or have Minnesota,” says Nathan Chomilo, M.D., for that child’s age and developmental stage,” books in the home, and their children’s lan- medical director of the Minnesota chapter. recalls Chomilo. guage development advances by three to six Because about 90 percent of children will The participating physician also gives par- months on average, according to data from be seen at least once by a pediatrician ents tips for making story time more engaging the national organization. One study pub- in the first year of life, he says, doctors and interactive, such as emphasizing rhyming lished in Clinical Pediatrics found that partici- have the chance to help families set the or, for older children, asking open-ended pating toddlers scored higher in receptive and read-aloud habit early on. questions. The “how” is important and it expressive vocabulary, regardless of parental varies by age, he says. “And there’s evidence education, parental language proficiency, behind it — this isn’t just a feel-good thing.” or foreign-born status.
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247683_MB Spring2019 PRINT.indd 28 4/8/19 11:36 AM Alumni Spotlight | Nathan Chomilo, M.D.
Poverty, racism, discrimination, those are all stressors. But there are also experiences that buffer that. The time that you feel safe
and loved with a trusted adult is one way STEVENS LYNDSAY PHOTO: to buffer against that toxic stress.
– Nathan Chomilo, M.D.
OFFSETTING STRESSORS That’s a big deal, Chomilo explains, because low liter- acy is linked to poverty, substance abuse, and crime later in life. And reading together as a family also has been shown to increase parents’ confidence in their parenting abilities — and help offset anxiety for both Jack Weston and his daughter, first-year medical student Julia Weston, child and parent. enjoyed Family Weekend festivities last fall. “Poverty, racism, discrimination, those are all stressors,” Chomilo says. “But there are also experi- ences that buffer that. The time that you feel safe and loved with a trusted adult is one way to buffer against Family Weekend (second annual!): that toxic stress. August – “This is why I wanted to become a doctor, to help improve my community,” he says. The Medical School invites students’ parents and other family members to ROR is one promising, relatively low-cost path to attend a series of informative and entertaining events August 22–23 during decreasing the state’s vast racial disparities — what Family Weekend. It’s a great time for families to connect with their students Chomilo calls “gaps in opportunity” — but it requires in their new surroundings at the Medical School while hearing from faculty buy-in from doctors and policymakers, Chomilo says. members and exploring the Twin Cities campus. The event culminates in the Physicians, already squeezed to do more in less time, White Coat Ceremony, during which new students receive their first white sometimes hesitate to add ROR to their practices. “But coats, at 2 p.m. Friday, August 23, in Northrop Auditorium. M|B almost universally, they find that it just fits seamlessly To learn more about Family Weekend, visit med.umn.edu/family-day. with their visits.” To find out more about the White Coat Ceremony, contact Rachel Rudeen Speaking of time, the self-described “citizen-physi- at [email protected] or 612-626-4519. cian” appears to manage it well. Besides his many other roles, Chomilo finds time to spend with family, serve as an adjunct assistant professor at the U of M Medical School, play adult league soccer, attend Vikings games, travel, and devour comic books. “I’m a big comic book nerd,” he admits. Not surprisingly, reading is a favorite pastime for the CELEBRATING 50 YEARS whole family. Chomilo’s 2-year-old son, Nchare, is cur- OF FAMILY MEDICINE rently into Please, Baby, Please by Spike Lee and a pic- Join us on Friday, October 11, as we celebrate ture book about trucks. “One of my proudest moments the 50th anniversary of the Department of in the past year was when he was around 16 months, Family Medicine and Community Health. M|B he went to the bookshelf, grabbed a book and brought it to me,” says the friendly doctor, as a broad smile Visit z.umn.edu/FMCH50 for more information. appears just above his bow tie. M|B
By Susan Maas, a Minneapolis writer and editor and a regular contributor to the Medical Bulletin
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247683_MB Spring2019 PRINT.indd 29 4/8/19 11:36 AM Scholarship Winner | Terri McBride
She changed her major to biology and PHOTO: SCOTT STREBLE SCOTT PHOTO: shortly thereafter was recruited into the Maximizing Access to Research Careers (MARC) and Research Training Initiative for Student Enhancement (RISE) programs, which give students from minority backgrounds research experience and mentor them toward careers in research. Among other things, the program sup- ported her attendance at a science conference where she presented a poster that caught the attention of Casey Dorr, Ph.D., a U of M gradu- ate who is now an assistant professor in the Medical School and a researcher at Hennepin Healthcare Research Institute. That connec- Charting her own course tion ultimately brought McBride to Minnesota for medical school. TERRI McBRIDE GREW UP in San Antonio, She quit school and enlisted with the Coast SERVING THE UNDERSERVED Texas, but she always dreamed of traveling Guard, eventually intending to take advantage And she’s still happy about her choice. “The the world. So in 1999, after joining the U.S. of the GI Bill to finance her education. “The administration has really been reaching out to Coast Guard as an active-duty member, she Coast Guard sounded attractive to me because students, getting feedback, and implementing was excited to accept a post as a boat crew- their missions are not combat-oriented,” it,” notes McBride, who is now in her third year man and watchstander on Long Island in McBride says. “They’re involved with search of medical school. “They’ve reduced the lec- New York. and rescue. They help protect the environ- ture hours, which sounds like a minor thing, Her duties were rigorous. ment. Those things are in line with my values.” but it’s huge for medical students, who can “It was a hard job,” McBride recalls. “We She also got to travel the world — visiting get really burned out. cleaned the boats. We sanded and painted Alaska, Mexico, Indonesia, Thailand, and many the boats. Our 24-hour watch days alternated other places — as part of the job. with 9-to-5 workdays.” In 2009, McBride left active duty and began Plus, she learned a lot about discipline. In work on a bachelor’s degree in nutrition some ways, you might say, it was perfect prep- science/dietetics at San Jose State University aration for the challenges of medical school. in California. She had been trained as a cook during her time in the Coast Guard, but FROM SEA TO SCHOOL academia introduced her to the science of For McBride, joining the Coast Guard was a nutrition — and it fascinated her. means to end. She had grown up in a poor community and, after graduating high school, decided to pursue a degree, becoming the I’ve always wanted to serve first in her family to attend college. But she soon found that balancing her studies with a the underserved because of my full-time job was difficult. background. I have a natural “The hours that I needed to work as a wait- empathy toward what some ress to make rent and pay tuition interfered with the time I needed for classes and home- people may consider “hopeless” work,” McBride says. patients. – Terri McBride
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New book marks ENT’s years at the U
“I’m also impressed by how open- working in the legal system with people A new book, Otolaryngology at the University of minded the faculty are as far as things who have mental illnesses and with other Minnesota: 1888–2018, chronicles the history of that they incorporate into their curriculum. underserved populations. ear, nose, and throat medicine and surgery and We’ve had a curriculum about race and “I’ve always wanted to serve the under- celebrates the specialty’s 130-year history at the medicine that I thought was very helpful. served because of my background,” she U of M — an anniversary that coincided with the Faculty have brought in LGBT and trans- says. “I have a natural empathy toward Medical School’s founding in the same year. gender community [members], and they what some people may consider ‘hopeless’ The book describes the talk about things that you wouldn’t neces- patients due to their lack of medical compli- evolution of the specialty sarily think of in the health care setting.” ance and self-harming behaviors, because and the Department of Oto- McBride has also benefited from I have experienced the same frustrations laryngology–Head and Neck financial support through medical school, with many of my family members. Surgery, highlighting the pro- including from the Alpha Epsilon Iota “Looking back, I can see that when gram’s rise to regional and Endowment Fund, which supports diversity people in our family or neighborhood national prominence. It was in the student body. got sick, they didn’t get top-notch care edited by ENT specialist Kent “Being an independent student, every because of our financial status. I want to Wilson, M.D. (a 1966 gradu- dollar counts for me,” she says. “Especially serve those people.” M|B ate of the Medical School), when I started medical school, I had so with assistance from Robert By Joel Hoekstra, a Minneapolis writer and editor much debt just from all the testing fees, Maisel, M.D. (1967), and tutoring fees, traveling.” To make a scholarship gift or to learn Thomas Christiansen, M.D. (resident alumnus, 1974). McBride still serves in the Coast Guard more, please contact Carrie Albers with What began as a specialty devoted to the health reserves as a finance and supply chief the University of Minnesota Foundation of eyes, ears, noses, and throats now includes exper- warrant officer and spends a good portion at [email protected] or 612-626-8481. tise in facial plastic and reconstructive surgery, of her breaks from medical school at the pediatric otolaryngology, and neurotology. M|B USCG Base Detachment St. Louis. She is Read the book for free online at z.umn.edu/ENThistory currently thinking about a career in foren- or buy the print edition at z.umn.edu/ENTbuy. sic psychiatry — a path that often involves
Capitol engagement
The University of Minnesota’s $87 million biennial budget request renovation. These “HEAPR” funds allow for system-wide updates to the Legislature this session focuses on attracting and keeping to improve campus safety, accessibility, and energy efficiency. the best faculty, improving equipment in research facilities, and With a new governor in place and the launch of a new budget supporting U of M outreach across the state. cycle, the University needs your help. Advocacy remains a key Topping the list is a requested $28 million state investment in component of our support: advocacy contacts made to elected the Institute of Child Development, built on the Twin Cities campus officials in 2018 increased by 94 percent over the previous year. in 1913. The $42 million bonding plan, which calls for the U to con- Clearly, our elected officials are hearing from you about the tribute $14 million, will turn the building into a modern research importance of the University to Minnesota. M|B and training hub for this top-ranked program. Please remain engaged and, if you haven’t done so already, To maintain its 29 million square feet of physical space, the Uni- join UMN Advocates at advocates.umn.edu/join. versity has requested an additional $200 million for asset repair and
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247683_MB Spring2019 PRINT.indd 31 4/8/19 11:37 AM Alumni Connections
A century of discovery A CENTENNIAL CELEBRATION SCIENCE FICTION AUTHOR Isaac Asimov once Many talented individuals wrote, “Everything about microscopic life is across the University have JULY 19, 2019 terribly upsetting. How can things so small be contributed seminal discov- Join us for a research symposium, so important?” eries over the past 100 years. luncheon, “Milestones in Microbiology” But “important” is almost too timid a word Here are a few standouts: presentation, and celebratory dinner. to describe the powerful microbes responsible Arthur T. Henrici, M.D. for some of humankind’s most devastating McNAMARA ALUMNI CENTER (1889–1943), called “Amer- diseases — tuberculosis, diphtheria, influenza, Learn more at z.umn.edu/microbiology100. ica’s bacteriologist” in his polio, HIV/AIDS, and staph and fungal infec- day, did pioneering work tions, to name just a few. on bacterial growth and Since the University of Minnesota’s Depart- structure, and provided ment of Microbiology and Immunology was one of the earliest descrip- established in 1918–1919, scientists there — and tions of the biofilms that play key roles Dennis W. Watson, Ph.D. (1914–2008), in other departments, too — have contributed in dental plaques, infectious diseases, developed the anthrax vaccine used to pro- mightily to the world’s store of knowledge and antibiotic resistance. tect soldiers in World War II, and was the about the bacteria, fungi, and viruses that first to identify the toxic component of teem within and on humans, animals, and Robert G. Green, M.D. (1895–1947), is Gram-negative bacteria, which can cause plants. In fact, the American Society for credited with saving the Midwest fur indus- fever, diarrhea, and toxic shock. Microbiology recently recognized the Univer- try through his studies of viral infections sity for its accomplishments over the past in silver fox and mink, and for discovering Martin Dworkin, Ph.D. (1927–2014), a pioneer century with a prestigious “Milestones in the first adenovirus, canine hepatitis virus, in understanding how multicellular bacteria Microbiology” award. and the vaccine that protected dogs and communicate and behave together, was foxes from it. among the first to apply mathematics Robert A. Good, M.D. (1922–2003), helped modeling to microbial research. PHOTO: COURTESY OF THE CENTER FOR THE HISTORY OF MICROBIOLOGY/ASM ARCHIVES lay the foundation for the first successful Current department chair and Regents Profes- human bone marrow transplant, performed sor Ashley Haase, M.D., two-time recipient of a at the U of M in 1968. National Institutes of Health MERIT Award for Lewis W. Wannamaker, M.D. (1923–1983), his work on HIV/AIDS, praises what he calls “a developed the strategies to prevent rheu- history of faculty excellence” in a department matic fever and kidney disease following a designed to teach students at every level, from strep infection that remain undergrads to medical and graduate students. the standard of care today. Now at home in a new building in the U’s Biomedical Discovery District, the department prepares students to take on the 21st centu- ry’s greatest infectious diseases. “Our rich, distinguished past has prepared CLOCKWISE, FROM TOP LEFT us well to work on the great killers of our Arthur T. Henrici, M.D. (third time,” says Haase, “including HIV/AIDS, TB, from left), and students take antibiotic resistance, and influenza.” M|B samples from Lake Alexander to study the bacterial ecology of lakes in 1932. Virologist Robert G. Green,
PHOTO: UNIVERSITY ARCHIVES
UNIVERSITY ARCHIVES UNIVERSITY PHOTO: M.D., in his lab circa 1940. The department found its first home in Millard Hall.
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A quality stethoscope for $? ALLISON THOMPSON PHOTO: If it seems like 3D printing is everywhere these Parts for the stetho- days, that’s because it is. And it’s good for scope were printed at more than simple modeling, as the U’s Bio- Makerspace using an Orig- Medical Library Makerspace is demonstrating. inal Prusa i3 Mk3 printer. Last year PLOS One published an article The stethoscope took by researchers who 3D-printed a functional, about four hours to print low-cost stethoscope. The research team says and used 57 grams of PLA Research teams have 3D-printed functional stethoscopes comparable to the their 3D-printed stethoscope was comparable plastic that cost $1.72. Littmann Cardiology III for a small fraction of the price. to the Littmann Cardiology III — which retails The nonprinted parts (ear- for about $100 and was the industry standard buds, silicone tubes, and until the newest model was introduced in a thin plastic sheet) were all generally to make an on-demand WEB EXTRA 2016 — and can be made for about $5. inexpensive and easily found. Assembly version that gives most They designed the stethoscope compo- took less than 15 minutes. of the functionality Find the printing nents using open-source computer-aided “Some of the greatest challenges in health at a small fraction of instructions at z.umn. design tools and made all the project files — care today are access and affordability. Our the price.” edu/stethoscope. from the original models to the printable students (and future physicians) need to learn The plans are freely parts to sound files used to test the stetho- to think critically and creatively, question available online and scope — freely available via a GitHub reposi- assumptions, and find new solutions,” says could be especially use- tory. The effort was part of a larger research Jonathan Koffel, a member of the U Libraries ful in resource-poor settings, Koffel adds. M|B project to design open, printable, and vali- team that 3D-printed and assembled a stetho- dated devices, including otoscopes, tourni- scope. “This is a great example of taking an quets, and pulse oximeters. iconic tool and using off-the-shelf technology
ACS HONORS U SURGEON
Henry Buchwald, M.D., Ph.D., a longtime professor Buchwald is also a professor of biomedical in the Department of Surgery and a Class of 1966 engineering at the University; his work developing resident alumnus, will be honored in June with the implantable medical devices has resulted in 2019 Jacobson Innovation Award for his ground- 17 patents. breaking work in metabolic/bariatric surgery. He was the first to hold the Owen H. and Sarah The award, bestowed by the American College Davidson Wangensteen Chair in Experimental of Surgeons (ACS), honors physicians who have Surgery, and in 2002 he received the Harold S. Diehl developed field-changing surgical advances. Lifetime Achievement Award from the Minnesota Buchwald is renowned for his surgical innovations, Medical Alumni Society. including the introduction of the partial ileal In 2020, the University of Minnesota Press plans bypass procedure to treat hyperlipidemia, or to release a memoir by Buchwald, tentatively Henry Buchwald, M.D., Ph.D. high cholesterol levels. titled A New Way. The book will explore the life An accomplished researcher, Buchwald in 1973 and work of Buchwald’s mentor, Owen H. Wangen- received the largest National Institutes of Health steen, M.D., Ph.D., the legendary surgeon who multicenter grant at the time, which funded a chaired the Department of Surgery at the Medical long-term study that proved a link between high School from 1930 to 1967. M|B cholesterol levels and heart disease.
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247683_MB Spring2019 PRINT.indd 33 4/8/19 11:37 AM Alumni Connections In Memoriam Mark your calendars
ALUMNI CELEBRATION: OCTOBER 11–12 Meeting their matches Join fellow alumni, faculty, and current students at this year’s Alumni Celebration, featuring a full day of tours THE McNAMARA ALUMNI CENTER and Medical School updates. Reunion dinners will be WEB EXTRA held for the classes of 1959, 1964, 1969, 1979, 1989, buzzed with excitement March 15 as 230 1994, and 2009. Watch for more details in the coming University of Minnesota Medical School See more photos from months. To update your contact information, visit students anxiously waited for the clock the big event at z.umn. med.umn.edu/alumni/stay-connected. to hit 11 a.m. It was Match Day, a culmi- edu/2019matchday. nation of four years of hard work and Help make your reunion memorable! The Medical determination — and the day they’d find School is seeking alumni to serve on the reunion plan- out what’s next on their journey to become doctors. ning committee or as reunion gift volunteers. M|B This year, a whopping 52.1 percent of the class matched to pri- To learn more about the Alumni Celebration and oppor- mary care residencies — a five-year high for U of M Medical School tunities to get involved, please contact Maureen Long at graduates. Following suit, the most popular specialties were family [email protected] or 612-626-8045. medicine (20.4 percent), internal medicine (19.1 percent), pediatrics (8.3 percent), and emergency medicine (7.4 percent), followed by INVEST IN THE NEXT GENERATION psychiatry, obstetrics and gynecology, general surgery, and internal medicine–pediatrics. Help us extend the University of Minnesota Medical More than 43 percent of those who matched will stay in Minnesota School’s legacy to the next generation of students by making a reunion gift or pledge in honor of your class. residency programs. M|B All gifts and pledges to the Medical School made between January 1 and December 31 by members of your class will count toward your class’ scholarship LEFT Caitlin Bell celebrates her gift total. You can also participate by documenting match in internal medicine at the or updating a planned or estate gift commitment University of Colorado School of this year. M|B Medicine in Denver. BOTTOM LEFT Nermine Abdel- For more information about making a reunion gift, updating your plans, or starting your own scholarship
PHOTOS: JOEL MOREHOUSE JOEL MOREHOUSE PHOTOS: wahab, here with her mother, Ekram Ahmed, matched to an fund, please contact Elsa Scheie at [email protected] internal medicine residency at or 612-625-7947. To make a gift online, visit z.umn.edu/ the U of M. reuniongift. BOTTOM RIGHT Jonathan Roberts and Sarah Kemp pause for a photo op.
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247683_MB Spring2019 PRINT.indd 34 4/16/19 7:41 AM Alumni Connections In Memoriam
EDITOR’S NOTE: The Medical Bulletin now DOUGLAS L. HOM, M.D., Class of 1974, Seattle, JOHN SONG, M.D., an associate handles obituaries for Medical School alumni in Wash., died Jan. 25 at age 69. Dr. Hom practiced professor in the Center for Bio- a new way. We are including simple announce- internal medicine. ethics and in the Medical School’s ments in print with a link to each person’s Division of General Internal Medi- LESLIE W. JACOBSON, M.D., Class of 1957, public obituary notice, when available, online. cine, died Feb. 27 in Minneapolis. Minneapolis, died Sept. 17 at age 86. Dr. Jacob- We provide links to published obituaries because Dr. Song was a talented teacher, son was an ophthalmologist. they offer readers the information families researcher, and clinician who was dedicated to have chosen to share to honor their loved ones. WAYNE H. JARVIS, M.D., Class of 1982, Duluth, health justice and equity and passionate about Full obituaries can be found at z.umn.edu/ Minn., died Nov. 15, at age 65. Dr. Jarvis was a addressing the needs of disadvantaged people. memoriam-spring19. general surgeon. He founded the Phillips Neighborhood Clinic in Minneapolis, a free clinic staffed by volunteers and LAWRENCE J. KLECATSKY, M.D., Class of students that serves those without insurance. CHARLES V. ALLEN, M.D., Class of 1958, 1967, Myrtle Beach, S.C., died Dec. 13 at age 77. Modesto, Calif., died Jan. 19 at age 85. Dr. Allen Dr. Klecatsky practiced emergency medicine. Read more at z.umn.edu/johnsong. practiced internal medicine. LOWELL H. KLEVEN, M.D., Class of 1958, Minneapolis, died Oct. 2 at age 85. Dr. Kleven ALAN M. AVRICK, M.D., Class of 1943, BRIAN D. SAINE, M.D., Class of 1967, Granger, was an orthopaedic surgeon. La Cañada Flintridge, Calif., died Jan. 12 at Ind., died Jan. 16 at age 76. Dr. Saine was an age 101. Dr. Avrick specialized in surgery and RANDALL A. LAKOSKY, M.D., Class of 1962, otolaryngologist. family medicine. Faribault, Minn., died Dec. 30 at age 82. JOHN M. SCANLAN, M.D., Class of 1963, Dr. Lakosky was a psychiatrist. MALCOLM N. BLUMENTHAL, M.D., Class St. Paul, Minn., died Oct. 26 at. age 81 Dr. Scanlan of 1958, Minneapolis, died Nov. 14 at age 85. CHARLES N. MARVIN JR., M.D., Class of 1981, was a psychiatrist. Dr. Blumenthal was an allergy and immuno- Wayzata, Minn., died Oct. 7 at age 64. Dr. Marvin logy specialist. MONICA A. SHERIDAN, M.D., Class of 1983, was a plastic surgeon. Walnut Creek, Calif., died Nov. 24 at age 66. JON E. BOLINE, M.D., Class of 1960, Highlands DUANE E. NESS, M.D., Class of 1958, Wadena, Dr. Sheridan specialized in physical medicine Ranch, Colo., died Sept. 15 at age 82. Dr. Boline Minn., died Nov. 10 at age 91. Dr. Ness practiced and rehabilitation. was a pathologist. family medicine. JOSEPH L. SPRAFKA, M.D., Class of 1945, EUNICE A. DAVIS, M.D., Class of 1954, St. Paul, S. SCOTT NICHOLAS, M.D., Class of 1961, St. Paul, Minn., died Oct. 14 at age 96. Dr. Sprafka Minn., died Jan. 28 at age 89. Dr. Davis was Minneapolis, died Oct. 17 at age 81. Dr. Nicholas was a surgeon. a pediatrician. was an allergy and immunology specialist. ANTON F. SPRAITZ JR., M.D., Class of 1957, JAMES H. DOBIS, M.D., Class of 1976, Lake WILLIAM F. NUESSLE, M.D., Class of 1946, St. Paul, Minn., died Sept. 16 at age 87. Dr. Spraitz Nebagamon, Wis., died Nov. 30 at age 69. St. Cloud, Minn., died Dec. 7 at age 94. practiced obstetrics and gynecology. Dr. Dobis practiced family medicine. Dr. Nuessle practiced internal medicine. BARBARA H. SUBAK, M.D., Class of 1955, Minne- RICHARD A. EDLUND, M.D., Class of 1956, Mus- ROBERT J. OLSON, M.D., Class of 1957, apolis, died Oct. 29 at age 92. Dr. Subak practiced kegon, Mich., died Jan. 31 at age 88. Dr. Edlund Williston, N.D., died Nov. 6 at age 87. Dr. Olson family medicine. practiced obstetrics and gynecology. was a radiologist. FRANK A. UBEL JR., M.D., Class of 1946, GILBERT H. FRIEDELL, M.D., Class of 1949, WARREN F. OSTLUND JR., M.D., Class of St. Paul, Minn., died Jan. 9 at age 94. Dr. Ubel Charleston, S.C., died Sept. 23 at age 91. 1968, Oakmont, Pa., died Sept. 26, at age 75. specialized in internal medicine and occupational Dr. Friedell was a pathologist. Dr. Ostlund was a radiologist. medicine. A. WILLIAM GEHRING, M.D., Class of 1965, JOHN A. PETERSON, M.D., Class of 1957, Rio DAVID A. VAN BOCKEL, M.D., Class of 1972, Hazen, N.D., died Jan. 15 at age 79. Dr. Gehring Verde, Ariz., died Aug. 20 at age 87. Dr. Peterson Louisville, Ky., died Dec. 2 at age 71. Dr. Van was a pathologist. was an anesthesiologist. Bockel was an anesthesiologist. DANIEL J. HANSON, M.D., Class of 1953, DEAN B. PRATT, M.D., Class of 1963, Elkhart STANLEY C. VON DRASHEK, M.D., Class of 1947, Toledo, Ohio, died Nov. 2 at age 90. Dr. Hanson Lake, Wis., died Oct. 29 at age 80. Dr. Pratt was Rio Verde, Ariz., died Dec. 19 at age 93. Dr. Von was a pathologist. a general surgeon. Drashek was a radiologist. KENNETH G. HENRY, M.D., Class of 1952, GEORGE E. REISDORF, M.D., Class of JEFFREY C. YUE, M.D., Class of 1986, Medina, Bloomington, Minn., died March 12 at age 98. 1960, Inverness, Fla., died Jan. 11 at age 83. Minn., died Jan. 10 at age 59. Dr. Yue was an Dr. Henry practiced family medicine. Dr. Reisdorf was an orthopaedic surgeon. anesthesiologist.
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247683_MB Spring2019 PRINT.indd 35 4/8/19 11:37 AM A Look Back Still pushing the limits
Center for Magnetic IN DECEMBER 2017, Kamil Ugurbil, Ph.D., and his MB: What made you UGURBIL: Before Resonance Research team at the University of Minnesota’s Center for think that high-field I came to academia, Magnetic Resonance Research (CMRR) produced the human imaging was I worked at Bell Labs director reflects world’s first MRI of the human body at 10.5 Tesla — possible when others in New Jersey, where on four decades a magnetic field strength 3.5 to 10 times greater said it wasn’t? we pioneered the use of advancements than today’s standard clinical MRIs. of nuclear magnetic In the early years of MRI, four decades ago, resonance to study metabolism inside a living cell, magnetic fields higher than approximately 0.25 Tesla demonstrating the ability to detect metabolites in were thought to be difficult and suboptimal. Even when 1.5 Tesla was proven feasi- vivo for the first time. We used very high magnetic ble, many scientists thought the technology would top out there. fields, albeit in small samples, with magnets typi- Not Ugurbil, who in May will receive the 2019 Institute of Electrical and Electron- cally used by chemists and biochemists. But we ics Engineers Medal for Innovations in Healthcare Technology for his groundbreak- were always thinking, “Wouldn’t it be nice to ing imaging research. We caught up with Ugurbil recently and asked him to reflect develop this technology to apply to humans?” on the advancements he’s seen — and pioneered — over the years. Difficulties predicted for human imaging were based on simulations and theoretical consider- ations that were not experimentally proven. Mag- netic resonance techniques are extremely dynamic, Proof that scientists extremely versatile. There was no reason to think can make the differ- ence: These are early that someday we wouldn’t be able to apply them 4 Tesla MR images to humans. taken by the manufac- turer, at left, and the MB: Tell us about your UGURBIL: We were CMRR, at right. first foray into human lucky that, in the mid- high-field imaging. 1980s, the U was look- ing to invest in some
IMAGE: COURTESY OF KAMIL UGURBIL, PH.D. OF KAMIL COURTESY IMAGE: new areas and solicited ideas from the faculty, analogous to what the Medical Discovery Teams program [a state-funded Medical School initiative] looks like today. We applied for and got that fund- ing. That’s how we got the 4 Tesla scanner.
CMRR 1982 1990 1992 1998 Kamil Ugurbil, Ph.D., arrives at the CMRR produces the CMRR introduces CMRR is first in the world to demon- Milestones University of Minnesota and starts world’s first high- functional brain imaging strate that breast tumors can be his laboratory (initially located on contrast, high-resolution for the first time, together detected through high-field magnetic Lake Minnetonka) focused on images of the human with independent and resonance imaging and spectroscopy. using magnetic resonance tech- brain at high magnetic concurrent work by nology that would eventually fields (4 Tesla and above). investigators from 1998 evolve into the Center for Mag- Massachusetts General CMRR moves to its new home, a netic Resonance Research (CMRR) Hospital, showing 36,000-square-foot facility in the on the Twin Cities campus. neuronal activity in University’s then-new Biomedical the human brain. Discovery District.
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247683_MB Spring2019 PRINT.indd 36 4/8/19 11:37 AM The Center for Magnetic Resonance Research’s first 4 Tesla scanner now only functions as art in the A Look Back building’s courtyard. “That’s the magnet that started this whole endeavor,” says longtime director Kamil Ugurbil, Ph.D.
HOW MRI WORKS
A powerful magnetic field and radio waves generate signals from hydrogen atoms in the body. Those
PHOTO: SCOTT STREBLE SCOTT PHOTO: signals are detected by a radio antenna and then translated by a computer Before the magnet came to Minnesota, Michael MB: Which of the UGURBIL: Generally into clear, 3D images of the Garwood, Ph.D., from CMRR already showed that, CMRR’s achievements speaking, we are very scanned area. contrary to expectations, one can get excellent are you most proud of? proud of our efforts to anatomical images of the human brain at 4 Tesla. push to higher mag- After the system arrived in Minnesota, the first netic fields. We developed the understanding of the thing we attempted was functional brain imaging, physics of imaging at high fields and the physics of which was successful. That was not only one of the functional imaging, which is intricately linked to first applications of human imaging on the 4 Tesla magnetic field strength. We developed technolo- WEB EXTRA
magnetic field, but also a new discovery — one that gies to overcome difficulties at high fields. We View more brain images from could actually image brain activity. This was a introduced 7 Tesla, and finally, today, we are at the CMRR’s 7T scanners at major development, a revolution. 10.5 Tesla. We developed the whole field, essentially. z.umn.edu/7T. We used to be the only ones doing this type of MB: Then you started UGURBIL: Today, the research. Today it’s a burgeoning research area. working on the 7 Tesla 7 Tesla is an instru- So a lot to be proud of, I guess! It’s a good way technology, which you ment you can buy. to start my day, talking about this! M|B literally built from the It wasn’t when we ground up. started. We were the Interview by Nicole Endres first in the world to put it together. The 7 Tesla is now FDA-approved for clinical diagnosis and is really the most advanced platform for human imaging that exists.
1999 2009 2010 2013 CMRR experts introduce CMRR is named a coleader of the CMRR expands to 75,000 BRAIN Initiative launches, the 7 Tesla MRI scanner National Institutes of Health’s square feet, providing with many studies using they developed for Human Connectome Project researchers and physicians imaging expertise developed human studies. (HCP), the most ambitious brain with new space. at the CMRR. imaging study conducted to date; 2009 CMRR develops all image acquisi- 2013 2017 16.4 Tesla scanner arrives tion and reconstruction tech- The 110-ton 10.5 Tesla CMRR produces the first- at the U for animal studies. niques employed in the HCP and magnet arrives at the CMRR. ever 10.5 Tesla image of its subsequent follow-up grants. the human body.
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