CONTINUED on page 4 MAKING GAINS ON PAIN Jim Sonner MD Since 1846 when ether was first used medically, doctors have administered anesthetics to control pain, anxiety and consciousness (awareness). You may be surprised to learn that anesthesiologists, who are very skilled at taking a patient through surgery, still do not know pre- cisely how anesthetics work. The long held view, based on a connection between anesthetic potency and lipid solubility, was that the anesthetic compounds acted on cell membranes (largely lipids) to exert their effects. After the 1980’s a new view surfaced, one that is prevalent today, that general anesthetic compounds act by binding specific receptors on nerve cells in the brain. Enter HMRI’s Dr. Jim Sonner. A Southern California na- tive, Dr. Sonner studied chemistry at Harvey Mudd Col- lege. After earning an NSF fellowship, he attended both Harvard University and Medical School for his graduate studies, and received his MD from Harvard. After being inspired by a charismatic anesthesiology chief resident Kevin King MD DEEP IN THE BRAIN CONTINUED on page 4 When Star Trek emerged as a cultural phenomenon in the late 1960’s, it not only transformed our vision for the future of intergalactic space travel, but it also offered a glimpse of potential technologies that could affect nearly every aspect of our daily lives. Among the many techni- cal marvels on the starship Enterprise was the “TriCord- er,” a handheld, noninvasive complete diagnostic pack- age waved over patients by the ship’s medicine man, Dr. McCoy. If you spend a few minutes with HMRI’s Dr. Kevin King, you’ll come to realize that the future is not as far away as it once seemed. While Dr. McCoy’s tricorder is years away, Kevin King’s ability to look deep within the processes of our bodies, particularly the brain, is taking shape today in Pasadena. Dr. King recently assumed the helm of HMRI’s Advanced Imaging & Spectroscopy Center. As Director of the Cen- ter, he will be building on HMRI’s exceptional legacy of MRI-based imaging research in anatomic imaging as well as chemical imaging (spectroscopy).
Transcript
INSIGHTSHMRIHUNTINGTON MEDICAL RESEARCH INSTITUTES
FALL 2016
CONTINUED on page 4
MAKING GAINS ON PAIN
Jim Sonner MD
Since 1846 when ether was first used medically, doctors have administered anesthetics to control pain, anxiety and consciousness (awareness). You may be surprised to learn that anesthesiologists, who are very skilled at taking a patient through surgery, still do not know pre-cisely how anesthetics work. The long held view, based on a connection between anesthetic potency and lipid solubility, was that the anesthetic compounds acted on cell membranes (largely lipids) to exert their effects. After the 1980’s a new view surfaced, one that is prevalent today, that general anesthetic compounds act by binding specific receptors on nerve cells in the brain.
Enter HMRI’s Dr. Jim Sonner. A Southern California na-tive, Dr. Sonner studied chemistry at Harvey Mudd Col-lege. After earning an NSF fellowship, he attended both Harvard University and Medical School for his graduate studies, and received his MD from Harvard. After being inspired by a charismatic anesthesiology chief resident
Kevin King MD
DEEP IN THE BRAIN
CONTINUED on page 4
When Star Trek emerged as a cultural phenomenon in the late 1960’s, it not only transformed our vision for the future of intergalactic space travel, but it also offered a glimpse of potential technologies that could affect nearly every aspect of our daily lives. Among the many techni-cal marvels on the starship Enterprise was the “TriCord-er,” a handheld, noninvasive complete diagnostic pack-age waved over patients by the ship’s medicine man, Dr. McCoy. If you spend a few minutes with HMRI’s Dr. Kevin King, you’ll come to realize that the future is not as far away as it once seemed. While Dr. McCoy’s tricorder is years away, Kevin King’s ability to look deep within the processes of our bodies, particularly the brain, is taking shape today in Pasadena.
Dr. King recently assumed the helm of HMRI’s Advanced Imaging & Spectroscopy Center. As Director of the Cen-ter, he will be building on HMRI’s exceptional legacy of MRI-based imaging research in anatomic imaging as well as chemical imaging (spectroscopy).
Why are we emphasizing physician-scientist leadership at HMRI? Because physicians have one way of looking at medical problems and scientists (without clinical training) have a completely different perspective. Putting both together yields more than 1 + 1 = 2 (a syn-ergism emphasized in HMRI’s current leadership structure). In theory the small numbers of students graduating with the combined MD/PhD degree are in the perfect position to rise to the top of of the medical research world. But the real world realities have meant that these valuable, highly-trained, cream-of-the-crop are often forced to choose one path over the other. Very few sustain a career of meaningful con-tributions to clinical care and to research. In 2014, the NIH studied this tragedy and the numbers are startling. The mean age of MD/PhD degree recipients at the time of their first independent funding is 44.3 years! Though medical schools are graduating large numbers of women—In 2015, 9798 men and 8907 women populated U.S. medical school student bodies—as of the 2014 NIH report only 22% of the MD/PhDs with NIH funding were women. Medical schools also have a remarkable glass ceiling at the highest academic rank where only about 20% of Full Professors are women. MD/PhD pro-grams are also not doing so well in attracting a broad distribution of ethnicities—In 2012, 68.4% of the dual degree awardees were white, 26.1% Asian, 3.2% Hispanic, 1.3% African-American, and <0.2% Native American.
What is going on? Well…it’s complicated! But when you start your academic career after residency (3-5 years minimum) which follows MD/PhD training (8 or more years), you are assigned clinical duties, and given an allotment of “academic time” for developing your re-search program. Unfortunately, that time is often minimal and clinical responsibilities overwhelm, plus the late 30’s are when families are started, and the MD/PhD is pulled in ten different directions. Finan-cial rewards for clinical time are often better than for research time, another stress.
At HMRI, we are committed to developing the careers of our incred-ibly talented physician scientists (old and young) – those with formal PhD training and those without – by supporting them as leaders in the lab. We are emphasizing clinically-inspired research by working to get them better resourced, and surrounded by a technical team that can execute for them. On the one hand, HMRI puts little administrative burden on researchers but on the other, our salary structure is poor compared to medical schools. In fact, our emphasis on physi-cian-scientist leadership is unusual especially for an independent non-profit, bucking the trends, but those of you who take the time to talk to our physician-sci-entist leaders will soon understand why this ‘line in the sand’ is so important, and why your support of HMRI makes a difference.
Our “Cross-Talk” interview series with HMRI re-searchers was started as a fund-raiser for the cap-ital campaign. The first two with Bob Kloner MD/PhD (cardiology) and Myron Tong MD/PhD (liver disease) highlighted the need for our stakeholders and donors to hear about our research in person—These investigators with a lifetime of clinical and research productivity are truly awe-inspiring! So if something in this Newsletter (say that article about Kevin King MD or Jim Sonner MD) piques your curi-osity, come and talk to our investigators, and join us in supporting our mission.
Marie Csete MD, PhDPresident & Chief Scientist
UNDER THE MICROSCOPEENHANCING THE PHYSICIAN-SCIENTIST WORKFORCE
Staff Leadership
Marie Csete MD, PhD President & Chief Scientist
Frank Davis MBA Vice President of Finance
Robert Kloner MD, PhD Vice President of Translation
Dave Silvey MBA Communications Officer
Board of DirectorsJohn L. Mothershead, ChairmanGeorge D. Leal, Vice Chairman
Jonathan F. AtzenHelen Baatz RN MAJohn BabcockJohn D. Baldeschwieler PhD, TreasurerC. Joseph ChangDavid DavisRoger EngemannJames J. Femino MDJames D. Gamb, SecretaryHerbert Hezlep IIILawrence W. Jones MDNelson D. JonesKathleen KaneSusan E. Kane PhDDaniel KimbellAllen W. Mathies MDRobert D. MayPeter M. MenardLary J. MielkeLynn H. MyersJames J. RhodesPhilip V. SwanWilliam E. ThomsonRobert E. Tranquada MD
EmeritusWilliam F. Agnew PhDMichael C. DoyleJerry M. HarringtonMitchell B. Howe JrR. William JohnstonRobert J. Mackin Jr PhD
INSIGHTS is published four times per year by Huntington Medical Research Institutes, a 501(c)(3) nonprofit organization dedicated to changing lives through multidisciplinary patient-focused research.
Born in 1916, Leo Bullara, long-time employee in HMRI’s Neural Engineering program, passed away a few months ago. Dr. Bill Agnew, retired HMRI Neural Engineering stalwart, filled us in on the life of this remarkable man, who joined forces with HMRI in 1966. Leo’s family were immigrants to Mexico from Italy, but Leo was orphaned as a child, and had a difficult early life. He was clearly a striver and received an undergraduate physics degree at USC, worked for a while in the aerospace industry and then had a long career at HMRI, where he was renowned for designing and fabricating a variety of devices for HM-RI’s neural prosthesis projects.
Dr. Agnew met Leo in 1965, the year Leo was inter-viewed, then hired by Dr. Robert Pudenz. In Bill Agnew’s words: Physiologists always have need of helpful gadgets not commercially available and frequently attempt fabri-cation themselves. Even though the gadgets may “work” they usually look like they were made by physiologists!! (Doug McCreery and myself will have to confess to be-ing guilty physiologists.) Leo (also known as Leoni around HMRI) took great pride in having a detailed plan with drawings and insisted that the instrument not only perform as needed but had a professional look when delivered. In other words he often turned our gadgets into instruments. I remember that Leo didn’t like “over the shoulder instruc-tions.” When considering a project he would say “let’s sit down I want to talk atcha.”
When Leo’s abundant talents were recognized, a base-ment lab in 734 Fairmount was made into a workshop. Leoni became friends with one of our board members, Collis H. Holladay (a nephew of philanthropist Henry Huntington) because of their mutual interest in workshops.
Not only was Mr. Holladay interested in Leo’s work but he donated several thousand dollars to equip it with a super lathe and all ancillary equipment. With HMRI’s low equipment budget at the time it was a very significant gift.
One example of Leo’s skill took place during our stud-ies on the blood-brain barrier and cerebrospinal fluid. He ingeniously used a record player, adding a circular platform with a ring of test tubes around it, to collect bi-ological samples from a catheter fixed in place. This de-vice allowed collection of uniform samples using a range of speeds. A second instance of Leo’s help on the same project involved modification of an ultramicrotome used for obtaining freeze- dried sections for examination under electron microscope. This effort resulted in a publication by Bullara and Agnew in Stain Technology in 1970. He also set up an FDA approved clean room in the basement for fabrication of electrodes to be used in human patients. Leo invented and held the patent on the HMRI Huntington Helix electrode and was the key man in the technolo-gy transfer to Cyberonics of Houston, Texas. Cyberonics personnel were trained by Leo at HMRI. Amazingly, Leo continued to work until his mid nineties (his last paper in PubMed from HMRI was published in 2007!).
Our current Neural Engineering staff all remember Leo as a compassionate, wonderful human being. The Bullara Family Singers were also talented outside of science and performed at HMRI Christmas parties. Finally, Bill Ag-new recalls: Our Leo always signed his drawings or re-ports with a row of numbers followed by the letters BGG. When I asked him about this he said the numbers were the numeric date and the letters stood for “By the Grace of God.” Bill Agnew told Leo that the language was “rem-iniscent of Columbus in the Caribbean” but nevertheless, “it was a neat and humble way to log off.”
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motivated his personal interest. What are the process-es that make memory possible? Why does it go wrong with some people more than others? How does storage of memory connect with our executive functions, our senses and motor functions? Dr. King is adding his own perspec-tive to HMRI’s ongoing Alzheimer’s disease study.
Kevin King got to thinking about his grandfather, who was a lifelong smoker. We know that smoking is a risk factor for heart and vascular disease, and that damage to blood vessels creates a ripple effect of pathology throughout the body. Dr. King’s MRI - based studies characterize this link between damage to the vascular system of the brain and Alzheimer’s disease. His particular focus is on the mi-crovasculature systems: an extremely delicate meshwork that stands as the final transit point in the vascular system before blood cells reach the capillary beds across which oxygen and nutrients are delivered to tissue.
In the brain, microvascular systems are highly vulnerable to changes in blood pressure because blood pressure in the brain is regulated distinctly from regulation in other organs. The brain demands a constant supply of blood, it uses about 1/5 of the heart’s output of oxygen. The brain does not have a large reserve of oxygen—cutting off oxygen to the brain is rapidly disastrous. To maintain the constant need for oxygen, large blood vessels that feed the brain remain in a sort of “constant maximum on” setting, meaning that they are always on full throttle, and so a consistently high pressure is placed on the brain’s microvascular networks.
In the HMRI imaging center, Dr. King is setting up a new way to study the reserve of blood vessels in the brain, a sort of stress test of the brain’s blood supply. These stud-ies will tell us a lot about the relationship of brain vascular disease to Alzheimer’s disease, and also tell us about the effects of heart disease on the brain, truly cross-disci-plinary research.
“In the short time that Kevin has been working with us, I have learned so much from him. He’s a fountain of excit-ing ideas that will inform work across HMRI, and connect us all to each other. We are enriched by Kevin’s strong training and recent experience as an investigator in the Dallas Heart Study, and by his talent for teaching,” says HMRI’s President, Dr. Marie Csete. Dr. King grew up in Texas, was an undergraduate at USC, then received his MD from Harvard Medical School in the Harvard-MIT Health Sciences and Technology program. He comes to HMRI after serving as an assistant professor at UT-South-western in Dallas and USC Keck School of Medicine. Welcome!
at Massachusetts General Hospital, Dr. Sonner continued his training as an anesthesiology resident at UCSF. Stay-ing at UCSF, he began dedicating more time to research, and advanced through the academic ranks to become a full Professor of Anesthesiology. Collaborating with the Pasteur Institutes Dr. Sonner set up experiments to test both theories of how general anesthetics work. He was guided by the concept that the correct theory should lead to identification of new anesthetics. The protein receptor model has not yielded new classes of general anesthetics, but Dr. Sonner has identified some potential new agents based on the cell membrane model (using tadpoles for the initial studies). To further his hunch of the importance of cell membranes in general anesthesia, Dr. Sonner also looked at diseases in which consciousness is blunted such as diabetic coma. In this case, the unconscious state is reversible, similar to general anesthesia. This pattern sug-gested that some “natural” compounds can be harnessed for use as anesthetics, perhaps replacing some of the synthetic (and sub-optimal) options currently available to anesthesiologists.
Dr. Sonner took a chance in changing his environment, hoping that HMRI would be a conducive place for ex-tending the promising initial studies of new anesthetics. Making the move to HMRI in June, he is thrilled to be working with long time friend Marie Csete, and is build-ing important collaborations with the strong neuroscience group led by Mike Harrington, including lipid biochem-ist, Alfred Fonteh. As is the case with most researchers at HMRI, Dr. Sonner is interested in what his research can also teach us about the fundamentals of the human body. His decoding of the mechanisms of anesthetics could lead to a better understanding of the basis of sleep and even help us understand why the cell’s energy machin-ery, mitochondria (with their own separate membranes), evolved within the cells of higher organisms. The work is likely to inform better options for treating epilepsy, and generally bolster understanding of the way information is processed in the brain. Dr. Sonner will be presenting these ideas in a public seminar in the Fall – The work is fascinating and profound, and could lead to long-needed change in the anesthesiologists’ toolbox.
MAKING GAINS ON PAIN
DEEP IN THE BRAIN Dr. King’s personal quest for knowledge began with his interest in understanding the links between human behav-ior and anatomy – or “psychobiology.” At the core of his inquiry is how the brain works to form memory, and how those processes deteriorate with disease. The expe-rience of seeing his grandfather’s death from Alzheimer’s
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65th ANNUAL HOME TOUR BENEFITS HMRI
On Friday, June 3rd, 2016, the members of the Altadena Guild gathered at the beautiful home of Andrea Morse-burg to present a check for $65,000 to Huntington Med-ical Research Institutes. The donation represented the proceeds from the 65th Annual Home Tour.
With a theme of “May Day on Porter,” this year’s home and garden tour took place on Sunday, May 1st and it focused on the magnificent homes and gardens on Alta-dena’s historic Porter Avenue.
Huntington Medical Research Institutes offers its thanks to everyone associated with this year’s event – from the Guild members who poured their hearts and souls into making the tour another success, to the owners of the exquisite homes and gardens featured during the tour, plus the volunteers, musicians, classic car exhibitors, and of course, the many sponsors and people who attended the event.
Special ThanksFor their extraordinary vision and leadership,
HMRI gratefully acknowledges the efforts of the 2016 Home Tour Co-Chairs:
Carolyn Artiaga
Suzy Burkhard
Priscilla Meyers
Linda Salinas
John and Genevieve Lucas are long-time donors and friends of HMRI. Their philanthropy reflects very personal family stories and a philosophy of seeding projects from the ground up. These are donors whose generosity makes such a difference to HMRI—as do their warm smiles and amazing sense of humor.
John and Genevieve are locals. Raised in Rancho Cu-camonga, Genevieve went to school with John’s broth-ers and met John while he was on home leave from the Navy. He was born in Pomona when this area was rural, and his parents owned Lucas Ranching Company. John’s great-grandparents had come to California with Gold Rush fever in the mid-19th century. Not finding the wealth of the gold they imagined, they returned to Germany. John’s grandfather then re-emigrated as a teenager to San Fran-cisco, working as a scout for Oregon Trail wagon trains. His mother was descended from Belgian farmers who came to America for land in 1815.
John attended the Naval Academy and served in the Pacif-ic during WWII, a shining example of the “greatest gen-eration.” He left the military for medical reasons (luckily recovered) and inspired by his lifelong love of math (and of course that family background) he went on to pursue a Ph.D. in Agricultural Engineering at UCLA. John received a post-doctorate fellowship from NIH and was sent to Berlin
for his research. Genevieve had never travelled there and admitted she was shocked to see the city wreckage in its post-war state. John later was a long-term employee of the Jet Propulsion Lab and has great stories to tell about the early space pro-gram spurred on by the US competition with the Soviets.
Genevieve studied nursing at Huntington Memo-rial Hospital in a joint program with USC. She worked as a nurse until her children were born (they have three), but continued in the great nurs-ing tradition, volunteering for 50 years at the American Red Cross.
An interest in science and technology ran in the family, and John’s brother Donald Lucas was an early investor in Oracle and later became its Chairman of the Board. In 1981 John’s brother Richard died of prostate cancer. From his estate the family started The Lucas Brothers Foundation. The foundation’s charitable giving included support of HMRI’s Dr. Larry Jones, a urologist and researcher who studies prostate cancer. The prostate cancer program at HMRI was a major beneficiary of the Lucas’ philanthropy and resulted in the creation of the prostate coil that is still in use to diagnose can-cer using MRI.
Other research areas of support came from deeply heart-felt interests. Genevieve’s mother died of Alzheimer’s disease. John’s brother was a football player at Stanford and now suffers from crippling dementia. John was quick to make the connection between the newspaper accounts of sports related traumatic brain injury and the link to later dementia. Results coming from the HMRI adult mild trau-matic brain injury program so impressed and disturbed HMRI investigators, that HMRI began a program to pro-vide free MRI exams of brain and heart to underserved student athletes in the Pasadena Unified School District. The program was spearheaded by Thao Tran, the lead technologist in HMRI’s imaging center. The passion of HMRI scientists and urgency of studying student athletes impressed the Lucases as well. John convinced the foun-dation to donate a much needed $100,000 award to sup-port the salaries of imaging staff and maintenance of the machinery involved in the PUSD study. The program was a feature of HMRI’s 2nd annual ‘Brain Day’ symposium at which the Lucases were honored. Further inspired by the results presented at Brain Day, the Foundation donated another $100,000 to support HMRI’s study of brain injury in children. The program is now expanding as a result of this gift. The wonderful compassion, generosity and in-volvement of John and Genevieve with HMRI is truly ap-preciated, and will blossom into a deep program of study of young brains exposed to trauma. John and Genevieve Lucas make a difference!
DONOR SPOTLIGHT: JOHN & GENEVIEVE LUCAS T H E L U C A S B R O T H E R S F O U N D AT I O N
The new building is the single most important step needed to propel HMRI’s best-of-its-kind, patient-focused research into the future. The building’s collaborative, multidisci-plinary framework will greatly enhance HMRI’s mission to discover better ways to prevent, diagnose and treat diseases for which good therapies do not exist.
The HMRI Forward Campaign continues to receive gen-erous gifts from supporters. So far, over $20 million in philanthropic support has been committed toward the $28.6 million goal needed to complete the campaign. Great work, everyone! While many naming opportuni-ties have already been reserved, several prominent op-portunities are still available, including the naming of the building, which will be visible on Fair Oaks Avenue.
Honor someone you love, admire or wish to re-member. Naming Opportunities in the new HMRI Biomedical Research Building include:
• Multiple Use Areas o Auditorium o Patient Waiting Area o Sustainable Garden o Medical Art Display o Conference Room o Convergent Space
• Laboratory Spaces o Cell & Tissue Biology o Liver Disease o Heart Disease o Diseases of Pregnancy
• Clinical Studies areas
• Scientists’ and President’s Offices
To learn more about the new building, and how to make the most advanced medical research part of your legacy, please contact Dr. Marie Csete at [email protected].
Thanks to everyone who is helping to make this project possible!
THE FUTURE IS UNDER WAYBuilding permits were approved in March; excavation for the Biomedical Research Building’s new foundation has started.
C. Joseph Chang
C. Joseph Chang has been an active healthcare executive in Greater Los Angeles hospitals for nearly 28 years. In the past 25 years, Joseph has served as the Administrator for Alhambra Hos-pital, Garfield Medical Center, and San Gabriel Valley Medical Center. He served as the President/CEO at Huntington East Valley Hospital in Glendora. In addition to hospital management, Joseph has participated in numerous health care projects such as free clin-ics, senior citizen centers and promoting awareness of preventive medicine. Joseph is active in many community affairs in Southern California. He has served on the boards of several civic and com-munity organizations including the American Heart Association, San Marino and Glendora Chambers of Commerce, Boy Scouts of America, the American Red Cross (recipient of the California Gold-en Bear Award for Exceptional Service in Inclusiveness in 2000), San Marino Public Library Foundation & Schools Foundation, and Los Angeles County Workforce Investment. Joseph was elected on to the Board of Education of San Marino Unified School District in 2001 and continues to serve. Joseph received his master’s degree in health administration from Tulane University in New Orleans, Louisiana. He and his wife, Shwu, reside in San Marino and have two sons with medical careers.
WELCOME TO THE NEWEST MEMBERS OF HMRI’S BOARD OF DIRECTORSTheir selfless service to our community
is an inspiration to us all
Jonathan Atzen
Experienced in representing publicly traded and private technology companies and entrepreneurs, Perkins Coie partner Jonathan At-zen has extensive experience advising on both public and private equity and debt offerings, mergers and acquisitions, and corporate governance matters. Jonathan regularly advises public companies in SEC reporting and compliance matters. In addition to represent-ing companies as outside corporate counsel, Jonathan’s career in-cludes serving as in-house general counsel to a venture capital fund and a publicly traded biotechnology company. Jonathan earned his B.A. in economics at the University of California, Santa Barbara and his J.D. at Loyola Law School. He currently resides in Pasadena with his family.
MISSION CHANGING LIVES THROUGH MULTIDISCIPLINARY PATIENT-FOCUSED RESEARCH.
HUNTINGTON MEDICAL RESEARCH INSTITUTES99 North El Molino AvenuePasadena, California 91101ADDRESS SERVICE REQUESTEDwww.hmri.org
