IN THIS ISSUE:
N IH grant advances quest for discovery
A ntibody inhibits Crohnâ€™s at early stage
John C. Reed among top doctors of the decade
The Burnham Report Winter 2006 Vol. 3, No. 1
Empowering our scientists to invent
In this issue... Winter 2006 Vol. 3, No. 1
NIH Grant Advances Quest for Discovery of New Medicines
Curbing Crohn’s Earlier in the Disease Process
THE BURNHAM REPORT
Protection at the Source of Neurodegenerative Diseases
John C. Reed, M.D., Ph.D., President and CEO
Dr. John C. Reed Named Among Doctors of the Decade
Karin Eastham Executive Vice President and COO Blair Blum Senior Vice President, External Relations Edgar Gillenwaters Vice President, External Relations Chris Lee Director, External Relations Nancy J. Beddingfield Editor, The Burnham Report www.burnham.org
The Burnham Report is published
four times each year by the Burnham Institute for Medical Research. We welcome your input. Please send comments or requests to be added to our mailing list for a printed copy of The Burnham Report, to email@example.com.
“Nanotechnology and the Life Sciences” Burnham’s 28th Annual Symposium
Foundations Unite to Aid Cancer Drug Discovery
Kozmetsky Family Gift Supports ALS Research
President’s Council Event: “The Creative Mind”
Fishman Fund Awardees for 2005
Meet the External Relations Team
Letter from Blair Blum
Donations – 4th quarter, 2005
The Legacy Society
Calendar of Events
10901 North Torrey Pines Road La Jolla, CA 92037 www.burnham.org
President’s message What’s in a name? “The Burnham Institute for Medical Research” tells who we are and what we do. We recently implemented this refinement from “The Burnham Institute”. We hope that our new name will better define us in the community and with you as we share the exciting news you read about our research in The Burnham Report.
In this issue, you will learn how it might be possible to “summon” antioxidants to the site of nerve damage, offering a new way to think about treating neurodegenerative diseases. You will learn that Dr. Hudson Freeze has discovered an antibody that inhibits Crohn’s disease in mice. The antibody acts at an earlier stage in the disease process than the most commonly prescribed treatment for human Crohn’s disease. Our cover story touches on how we intend to use some of these new discoveries as we build a resource that will enable the screening of promising drug targets against a collection of 2,000,000 chemicals. Our donors and our community are recognized in a new feature, “Philanthropy Matters”, debuting as an insert in this issue of The Burnham Report. You are reading this message from the first edition of The Burnham Report published as a virtual magazine, now available through electronic media. This virtual format provides extended coverage of items published in The Burnham Report via links to our website, which you can access 24/7. Join us any time at www.burnham.org! John C. Reed, M.D., Ph.D. President and CEO
Multimillion-Dollar NIH Grant Advances Burnham’s Quest for Discovery of New Medicines
Burnham has been selected by the National Institutes of Health (NIH) as one of nine national centers for high-throughput chemical compound screening, known collectively as “The Molecular Libraries Screening Centers Network” that will comprise the world’s largest collaborative network focused on drug discovery. Researchers at Burnham will be part of the world’s largest collaborative network focused on drug discovery, thanks to a $11.9 million grant from the National Institutes of Health. The NIH has selected Burnham as one of nine centers across the country for high-throughput chemical compounds screening, known collectively as the “Molecular Libraries Screening Centers Network.” This three year grant will be used to establish the San Diego Center for Chemical Genomics (SDCCG). As a member of this national screening network, Burnham will have access to a collection (“library”) of two million chemicals, which will be individually tested for possible future medications. Burnham researchers hope to uncover specific chemicals that interact with and inhibit diseasecausing proteins.
“The selection of Burnham and our partner organizations to serve as one of the nine national centers for this exciting initiative, validates our decision made over five years ago to build an innovative drug discovery infrastructure that empowers our scientists to go beyond basic discovery research and invent the new medicines of the future,” says Dr. John C. Reed, Burnham’s President and CEO, and Director of SDCCG. Burnham’s screening network will include a multi-disciplinary team of experts in biology, chemistry, engineering, physics, and computer sciences. Promising chemicals identified by robotic screening will be optimized for potency and safety using cutting-edge methods of structure-based drug design. The screening center employs and develops advanced instrumentation and methods for high-throughput automated
Nicholas Cosford, Ph.D., Project Manager, is a medicinal chemist and a former team member at Merck, Inc. Kristiina Vuori, M.D., Ph.D., is Deputy Director of the San Diego Center for Chemical Genomics and Acting Director of the Burnham’s NCI-designated Cancer Center.
microscopy, allowing for cell-based screens using high content imaging, as well as developing methods in Nuclear Magnetic Resonance (NMR)-based drug design, 3D computational modeling, and combinatorial chemistry. Information generated by the screening centers will be made available to the public and private sectors through a database maintained by the National Library of Medicine at NIH. This tremendous collaborative effort is expected to accelerate our understanding of biology and disease mechanisms, and enable academic researchers to explore novel ideas that will expedite progress on a broad front against human disease. Click here to learn more.
Curbing Crohn’s earlier in the
Geetha Srikrishna - Ph.D., Staff Scientist Hudson Freeze - Ph.D., Professor and Director, Glycobiology Program
A collaboration led by the Burnham Institute for Medical Research has discovered an antibody that binds to an unusual sugar molecule residing in the gut that halts the inflammation seen in Crohn’s disease and other intestinal inflammations. The antibody could prove to be a promising drug target for these common chronic intestinal disorders.
Dr.Dr. Freeze hashas found Freeze found anan antibody that inhibits antibody that inhibits Crohn’s at at anan earlier Crohn’s earlier stage in in thethe disease stage disease process than treatments process than treatments currently available. currently available. Professor Hudson Freeze, Ph.D., Director of Burnham’s Glycobiology Program, together with staff scientist Geetha Srikrishna, Ph.D., and other colleagues, found that a sugar chain normally present on white blood cells and intestinal cells plays a role in inflammation associated with Crohn’s, also known as inflammatory
bowel disease. The team then discovered an antibody that inactivates this sugar and inhibits the inflammation. The antibody was tested in an animal model for Crohn’s as part of a project supported by the Broad Medical Research Program of The Eli and Edythe L. Broad Foundation and the National Institutes of Health. “There are a large number of signaling molecules that are activated in inflammation,” said Freeze. “Antibodies against these sugar chain molecules, however, appear to curb inflammation before cytokines associated with inflammation, like TNF, are produced. The sugar chain must be used at an earlier stage, but in a more specific manner.” The sugar chain’s specificity could be crucial to developing treatments for Crohn’s and other inflammatory disorders. The body’s inflammation response usually is a healthy reaction to harmful foreign agents; inflammation disposes
of pathogens before they cause disease. Crohn’s disease and other inflammatory bowel diseases, generally known as auto-immune disorders, are a result of the body’s immune system overreacting to microbial pathogens, causing the body to attack its own tissues. The optimal treatment would inhibit excessive inflammation linked with disease, leaving normal immune function unaffected. The antibody, Freeze suggests, could prove to be an effective remedy for autoimmune disorders if it can act specifically on hyperactive inflammation, while preserving the immune system. Remicade™, an antibody-based drug currently used for Crohn’s, works by inhibiting the cytokines that are summoned into action at a later phase of these diseases. Click here to learn more.
Protection at the source of neurodegenerative diseases Very recently, Stuart A. Lipton, MD., PhD., Scientific Director of the Center for Neuroscience and Aging, discovered a way of inducing nerve cells in the brain and spine to release natural antioxidants. Antioxidants protect nerve cells from stress and free radicals, wich contribute to acute and chronic neurodegenerative diseases, such as stroke, Alzheimer’s disease, and Lou Gehrig’s disease. Working together with colleagues at Burnham and in Japan (Iwate University, Osaka City University, Gifu University, Iwate Medical University), Lipton reported in the Proceedings of the National Academy of Sciences that NEPPs (short for NEurite outgrowth-Promoting Prostaglandins) were able to activate a pathway that protects nerve cells from oxidative and nitrosative stress, which produces free radicals. This pathway, known as the Keap1/Nrf2 cascade, regulates the production of natural antioxidants, such as bilirubin, that can protect against
This discovery shows that it is possible to induce the release of specific antioxidants directly in nerve cells, at the site where damage and degeneration occurs. oxidative stress from ischemic stroke and degenerative disorders. These new drugs accumulate specifically in nerve cells, leaving unaffected cells alone. “This is the first reported evidence that this protective response can be activated directly in nerve cells to release antioxidants and counter oxidative stress,” said Lipton. “These findings provide support for further investigation of NEPPs drugs to potentially treat ischemic stroke, multiple sclerosis, Alzheimer’s disease, Lou Gehrig’s disease and other neurodegenerative disorders.” Click here to learn more.
Stuart A. Lipton, M.D., Ph.D. Director, Del E. Webb Center for Neurosciences and Aging at Burnham
John C. Reed Named Among
Top Doctors of the Decade Dr. John C. Reed, President and Chief Executive Officer of the Burnham Institute for Medical Research, was listed among the â€œDoctors of the Decadeâ€? in the January/ February 2006 issue of Science Watch, the bimonthly newsletter published by Thomson Scientific that tracks trends and performance in basic research. With 23,729 citations, Dr. Reed was ranked as the most cited author in the field of general biomedicine, a broad field of medicine that emphasizes principles of natural sciences including biochemistry, and biology. Dr. Reed was also listed as the 8th most cited doctor overall in clinical medicine, which includes fields of epidemiology, cardiology, and oncology, in addition to biomedicine. The study was based on papers published and cited in journals monitored by Thomson Scientific between 1995 and 2005. Click here to learn more.
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“Nanotechnology and the
Burnham’s 28th Annual Symposium | April 13 –14, 2006
engineering, and phototronics. This symposium is open to the public. For program, information, or to register on line, please visit www.burnham.org.
28th Annual Symposium Co-hosts: Dr. Erkki Ruoslathi, M.D., Ph.D., Distinguished Professor and former President and CEO at Burnham Jeffrey Smith, Ph.D., Professor and Director,
Nanotechnology is poised to transform medical diagnostics, medical imaging, and treatment of disease, and it could usher an era of personalized medicine. Building tiny machines to identify tumors and deliver drugs, clear arteries of dangerous plaque, or determine the presence of diseases, are just a few of the possibilities that scientists are now investigating. At Burnham’s 28th Annual Symposium, experts in the field will discuss the opportunities and challenges involved in creating devices of “nanoscale” that can detect diseased cells in the body or deliver drugs. Topics will include targeting, nanofabrication,
Nanotechnology and the Burnham The National Institutes of Health recently singled out Burnham as a “Program of Excellence in Nanotechnology”, awarding $13 MM to support a five-year project that will use nanotechnologies in the design of new approaches to detect, monitor, treat, and eliminate “vulnerable” plaque, the probable cause of death in sudden cardiac arrest. This project is made possible by use of targeting peptides discovered by Dr. Erkki Ruoslathi that were used in the first successful delivery of a nanomachine into living tissue. Dr. Jeffrey Smith, at Burnham, directs this consortium of 25 scientists from Burnham, UC Santa Barbara, and The Scripps Research Institute. Click here to learn more.
Program of Excellence in Nanotechnology
Dr. Ruoslahti has teamed up with nanoengineers to integrate “homing” functionality into nanodevices, or so called “mother ships,” capable of delivering diagnostic or therapeutic cargo to cancer blood vessels. This collaboration, based at UC San Diego’s Rebecca and John Moores Cancer Center, was recently recognized as a “Center of Cancer Nanotechnology Excellence” by the National Cancer Institute, receiving a five-year award of $20 MM. Click here to learn more.
Seed funding, such as the grants provided by these two foundations, plays a critical role in launching innovative projects that are not yet sufficiently developed to be competitive for NIH or other government funding.
National Foundation for Cancer Research and The Prostate Cancer Foundation Unite with Burnham Institute to Expedite Cancer Drug Discovery. The National Foundation for Cancer Research (NFCR) has aligned with The Prostate Cancer Foundation to grant $200,000 in seed funding to Burnham’s NCI-designated Cancer Center to develop three-dimensional experimental culture systems that simulate a tumor’s microenvironment. The outcome of this pilot study is anticipated to provide a new model for discovery and pre-clinical evaluation of anticancer drugs. Burnham investigators have developed a unique technique for culturing cancer cells into clusters, called spheroids.Threedimensional culturing of cancer cells is a significant advancement over conventional tissue culture methods in which cells are grown in two-dimension, as a flattened
layer on plastic. The new method will expedite the drug discovery process, as thousands of chemicals can be tested in three-dimensional cell culture to determine prime drug candidates before testing in animals. The NFCR and Prostate Cancer Foundation partnership funding will enable Burnham investigators to establish standards for threedimensional culture, which has potential applications beyond cancer, and develop new methods for high-throughput screening with chemical compounds and highthroughput imaging of spheroids. Click here to learn more.
Kozmetsky Family Gives $1 Million To support ALS research at Burnham Institute for Medical Research Funding will seed stem cell studies on Amyotrophic Lateral Sclerosis
LA JOLLA, CA. A $1 Million gift from the Kozmetsky Family of Austin, Texas will enable scientists at the Burnham Institute for Medical Research to incorporate human stem cells as a resource in their work on Amyotrophic Lateral Sclerosis (“ALS”). The gift, which originates from Ronya Kozmetsky and Cindy and Greg Kozmetsky, will provide seed funding to investigate the potential of stem cell therapy replacement as a potential treatment for ALS. “We are grateful to the Kozmetsky Family for their generosity and for placing their faith in Burnham’s researchers,” said Dr. John Reed, President and CEO. “The stem cell field, in its infancy, holds great potential for
ALS and other diseases. The Kozmetsky Family’s vision and courage makes it possible for us to move forward without delay.” “We know that important work on ALS is being held up for lack of funding. Our family is proud to be able to give in a way that makes such a difference”, said Cindy Kozmetsky, Vice President and Secretary to the Kozmetsky Family Foundation and Trustee at the Burnham Institute for Medical Research. ALS, also known as “Lou Gehrig’s Disease”, is the most aggressive of neurological diseases, claiming the lives of its victims within five years of diagnosis. Approximately 8,000 new cases of ALS are diagnosed each year, and 30,000 people throughout the U.S. currently have the disease. Nearly 100% percent of ALS patients die within three to five years; there is no cure for this disease and treatments are limited.
Despite the horrific suffering endured by ALS patients, pharmaceutical companies categorize ALS as an “orphan” disease because of its relatively small patient population, and generally do not invest in the basic research needed to lay the foundation for new treatments and, ultimately, a cure. The Burnham, together with other not-for-profit research organizations, performs high-risk discovery research needed to drive progress for ALS and other orphan diseases.
Awardees for 2005
“The Creative Mind”, President’s Council Event, spring, 2006 Dr. John Reed, Burnham’s President & CEO, Dr. Joe Sorge, Inventor, President & CEO, Stratagene, Ms. Sunna Bohlen, artist, Dr. Roger Guillemen, Moderator and Nobel Laureate, Jeff Thayer, Concert Master, San Diego Symphony, Dr. Stuart Lipton, Director, Del E. Webb Center for Neuroscience & Aging at the Burnham.
An important part of Burnham’s mission is training the next generation of scientists. The Fishman Fund, named in honor of Burnham’s cofounders Dr. William H. and Lillian Fishman, supports the promising research of graduate students and postdoctoral fellows training at the Institute.
Members of The President’s Council at the Burnham Institute for Medical Research were treated to an art reception and insightful panel discussion on “The Creative Mind” in March. Four panelists including a scientist, inventor, artist and musician joined moderator and Nobel Laureate, Dr. Roger Guillemin, to explore the biological and behavioral nature of creativity. Seated on the panel were Sunna Bohlen, visual artist and poet; Stuart Lipton, M.D., Ph.D, Neurologist, Director of the Center for Neuroscience and Aging Research at Burnham Institute for Medical Research; Dr. Joe Sorge, Inventor, President & CEO of Stratagene; and Jeff Thayer, violinist and concertmaster of The San Diego Symphony. The mission of the President’s Council is to recognize the simple fact that extraordinary generosity makes for extraordinary science. Philanthropic support from donors at the $1,000 and over level helps us to recruit leading scientists, launch the careers of promising young scientists, purchase state-of-the-art technology, and launch pilot projects. To find out more about membership in The President’s Council, contact Patty Fuller at (858) 713-9931 or via email at firstname.lastname@example.org.
Front: Nicole K. Noren, Ph.D., Lillian Fishman, Ruchi Bajpai, Ph.D. Rear: Lionel Hebbard, Ph.D., Ramon Diaz Trelles, Ph.D., John Stebbins, Ph.D.
Click here to learn more.
Meet the External Relations Team From left to right: Patty Fuller – Manager, Donor Relations/Planned Giving Blair Blum – Senior Vice President, External Relations / Administration and Major Gifts Edgar Gillenwaters – Vice-President, ExternalRelations / Principal Gifts Chris Ayson – External Relations Coordinator/ Prospect Researcher Chris Lee – Director, External Relations / Major Gifts and Annual Programs Robin Olson – Donor Management / Annual Fund Coordinator Kirstin Broome – Donor Relations / Event Coordinator
Letter from Blair Blum Dear friends of the Burnham Institute for Medical Research: I joined this great institute in the beginning of December last year and feel it is a great privilege to be a part of a mission that has the ability to change all of our lives...to perform outstanding basic research in the life sciences. All the areas of our research that I am learning about, will make a difference for many of us in both longevity and quality of life. Years ago, if I had heard what is common language at Burnham, I would have said it was science fiction “talk” but now I realize that this work will unlock the mysteries of so many diseases. As I remember the diseases that have affected my family and friends, I can now look to the day when we won’t have to worry so much about those afflictions. Healthcare is usually improved by what is coined a “disruptive innovation”; cure is defined by discovery. Some discoveries are actually made while working on another hypothesis and lead to clinical trials and new drugs. Your financial support of our work will help us continue to act on our ideas and make today’s dreams tomorrow’s reality. Your help allows us to recruit world class scientists, to purchase necessary lab equipment, and to challenge ourselves to find innovative approaches to discovery. Philanthropy will supply the funding necessary to complement our federal grants and guarantee that we will be able to deliver on our promise to you...From Research, the Power to Cure. Your past support has meant so much to us. Please continue to give us your vote of confidence. If you are just joining our donor family, please know what a difference your gift will make. I look forward to meeting you and to personally thanking you for your support. Warm regards, Blair Blum Senior Vice President, External Relations email@example.com
Fourth quarter 2005
In the last quarter of 2005, the Burnham Institute for Medical Research received 174 generous gifts totaling $1,850,821. The following lists individuals, foundations, and corporations whose giving was $5,000 or more. We are grateful for these gifts that support our many areas of research. Individuals Mr. & Mrs. David Begent Mr. & Mrs. Robert H. Boemer Mr. & Mrs. Lawrence Bloch Mr. Arthur Brody Mr. & Mrs. Matt Brower Mr. & Mrs. Michael Coit Mr. & Mrs. Andrew Dumke Mr. & Mrs. Karin and Gary Eastham Mr. Carlton J. Eibl and Ms. Amy Corton Mr. & Mrs. Kurt Eve Mr. & Mrs. Alan Gleicher Mr. Manual Gleicher Mr. & Mrs. Frank Goldberg Mr. Morley Golden and Ms. Deana Golden Ms. Lynn Gorguze and Mr. Scott Peters Mr. & Mrs. Fernando Gutierrez Mr. & Mrs. Han Helders Mr. Alan Hunter Ms. Jeanne Jones Mr. & Mrs. Ron Judy Mr. & Mrs. Leon Kassel
Mr. & Mrs. Greg and Cindy Kozmetsky Mrs. Ronya Kozmetsky Mr. & Mrs. J. Robert Lauer Mr. & Mrs. Jeff and Sheila Lipinsky Mr. & Mrs. Gregory T. Lucier Mr. John Liss and Ms. Lucy Anderson Mrs. Bobbie Jo MacConnell and Mr. Guy Showley Mr. & Mrs. Nicolas and Caroline Nierenberg Dr. & Mrs. Norman Neureiter Mr. Doug Obenshain Mr. & Mrs. Roy Polatchek Mr. Mark A. Pulido and Ms. Donna J. Walker Dr. John C. Reed and Ms. Muffy Walker Mr. & Mrs. Mike Rosen Mr. & Mrs. Aaron and Cynthia Shenkman Mr. & Mrs. Scott and Judy South Mr. & Mrs. Alan Stanford Mr. & Mrs. Eugene L. Step
Mr. & Mrs. Stuart Tanz Dr. & Mrs. Andrew and Erna Viterbi Ms. Carolyn Wheeler Mr. and Mrs. Jack White Anonymous Foundations Del E. Webb Foundation Leon Strauss Foundation Lipinsky Family Foundation Margot Anderson Brain Restoration Foundation Melvin Garb Foundation RGK Foundation Corporations Avanti Polar Lipids, Inc. Cleveland Biolabs, Inc. DBC Construction Invitrogen Corporation Novartis Pharmaceuticals Corporation Roslin Institute Serologicals
Burnham Wishlist The Institute is currently creating two shared facilities to provide new technology to our scientists. Instead of requiring large new instruments, these facilities take advantage of powerful new molecular approaches that enable investigators to assess or block the function of virtually any gene in a cell. The first facility uses RNA interference, where small, specific pieces of synthetic RNA are introduced into cultured cells. These short interfering RNAs (siRNAs) find their exact matching target RNA and specifically cause the shut-off of a single gene in the cell. Such an experiment previously took a year and cost many thousands of dollars, but Burnham scientists can now test the function of a gene suspected of contributing to disease in a few days. The new shared laboratory will accelerate the process, as investigators will be able to use “libraries” of siRNAs to determine the function of thousands of genes in normal cell function and disease. Equipment needed for the laboratory:
The second new facility is for Lentiviral Vectors. These modified viruses have been created to efficiently carry any new gene into a cell, where this gene then becomes part of the cell’s DNA. This ability to put a new gene into almost every cell in a culture is valuable for many scientific approaches, including understanding stem cell differentiation, and testing if diseases are caused or can be corrected by expression of a single protein. These viral vectors are also widely used to express interfering RNA to shut off genes permanently in growing cells. Although these vectors are designed so that they can not replicate in humans, they must be handled with caution. The lentiviral lab will create a central enclosed facility dedicated to work with these viral vectors. An expert in the facility will also accelerate the scientific progress of the many laboratories just starting in this field, while maintaining a safe environment. This one-room dedicated lab cannot share equipment with others, and needs:
Tissue culture incubator $6,000 Tissue culture hood $9,000 Microcentrifuge $2,000 Microscope $2,200 Multichanel Pipetter $900 Bar code reader $1,000 Microplate sealer $1,200 Tabletop Centrifuge $7,000 Electroporator $5,000
Tissue culture incubator $6,000 Biosafety cabinet $9,000 Microcentrifuge $2,000 Ultracold -80° freezer $7,000 Refrigerator/Freezer $900 Sealed Benchtop Centrifuge $9,000 Fluorescence microscope $7,000 Microscope Camera $2,600 BioSafety transport containers $400 Computer $1,200 For more information, please call Claire Hill at (858) 713-6277 or firstname.lastname@example.org.
Your planned gift today will place financial resources in the pipeline for future generations.
Private support for the Burnham Institute for Medical Research has never been more critical. Government funding is less predictable than in the past and we want to continue forging frontiers in the war against disease. Our scientists need your help. They depend on the generosity of individuals passionate about eradicating diseases â€“ not just in their own lifetime, but for future generations. The Legacy Society is a group of benefactors that have made provisions in their wills to support research at Burnham. Your planned gift today will place financial resources in the pipeline for tomorrow. There are no membership fees or minimum gift requirements. You may choose to designate your gift to help find a cure for a specific disease that has touched your life, or as an unrestricted gift to support our medical research. There are many creative ways to leave a legacy. Whether you choose to donate afterâ€Żyour income is no longer needed, leave a bequest, or would like to find out more about tax-saving gifts that return income today, please contact Patty Fullerâ€Żat (858) 713-9931 or email@example.com.
Calendar of Events 28th Annual Symposium: “Nanotechnology and the Life Sciences” April 13-14, 2006, 8:00 am – 5:00 pm Hilton La Jolla Torrey Pines (Information & Registration available on line at www.burnham.org.)
Community Open House Celebrating Burnham’s 30th Anniversary June 21, 2006, 5:30 – 7:30 pm Chairmen’s Hall at Burnham
Burnham Community Lecture Series: “Stem Cell Therapy for Diabetes: Prospects and Problems” August 8, 2006, 7:00 pm Dr. Fred Levine, Adjunct Professor, Stem Cells & Regeneration Program Fishman Auditorium at Burnham (This is a free lecture series, for the general public.) For more information about these events, please contact Claire Hill, (858) 713-6277, firstname.lastname@example.org. You can subscribe to The Burnham Report as a virtual magazine, by email to email@example.com
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