TABLE OF CONTENTS
- What is the Hereditary Disease Foundation (HDF)?
- How are the HDF's Business Operations and Fundraising Efforts Structured?
- How is the HDF Regarded in the Scientific Community?
- How is the HDF Unique?
- What are the HDF Scientific Programs?
- How Would my Money be Used?
- How Does HDF Benefit Advancements in Other Disease Research?
- Why Give to HDF?
1. What is the Hereditary Disease Foundation?
In 1968, a biomedical detective story began with one family's personal heartache. It eventually stretched from the poorest villages of Venezuela to the most advanced research laboratories in the world.
The Hereditary Disease Foundation (HDF) aims to cure genetic illness by supporting basic biomedical research. The HDF was started by Dr. Milton Wexler in 1968 when his wife was diagnosed with Huntington's disease (HD). The Foundation uses a variety of strategies – workshops, grants, fellowships, and targeted research contracts – to solve the mysteries of genetic disease and develop new treatments and cures.
Huntington's disease is a fatal, dominantly inherited, genetic, neurological disorder causing involuntary movements, severe emotional disturbance and progressive cognitive loss over ten to twenty years. Each child of an affected parent has a 50% risk of inheriting HD, usually in the third or fourth decade of life, though children as young as two years and adults in their eighties may also develop symptoms.
The Hereditary Disease Foundation uses Huntington's disease as a model for hereditary disease research because it is triggered by a mutation of one single gene. Progress toward treatment or a cure could be instrumental in finding ways to treat other illnesses with more complex genetics, including Parkinson's, Alzheimer's and Lou Gehrig's disease (ALS), depression, schizophrenia, and cancer.
The Hereditary Disease Foundation has spent over $60,000,000 to support pioneering research in genetics, gene therapy, molecular and cell biology, cell survival and death, animal models, neurophysiology, neuropharmacology and other areas relevant to the understanding of inherited diseases.
The Hereditary Disease Foundation played a key role in the discovery of the HD gene, which was localized in 1983 and isolated in 1993. The HDF recruited and supported more than 100 scientists worldwide who worked together as the Huntington's Disease Collaborative Research Group in a ten-year search to capture the gene.
The New York Times called the quest for the HD gene “legendary in less than a decade”; the gene, itself, the most “coveted treasure in molecular biology.”
New technologies developed during the HD gene search - supported by the Hereditary Disease Foundation - have been widely used in mapping genes for other disorders including cystic fibrosis, Parkinson's, Alzheimer's, cancer, heart disease and mental illness. These successes helped to launch the Human Genome Project.
Nancy Wexler, President
Nancy Wexler, Ph.D., is Higgins Professor of Neuropsychology in the Departments of Neurology and Psychiatry of the College of Physicians and Surgeons at Columbia University, as well as the President of the Hereditary Disease Foundation.
Involved in public policy, individual counseling, genetic research, and federal health administration, she is most widely known for her important scientific contribution on Huntington's disease.
Since 1979, Dr. Wexler has led a research study of the world's largest family with Huntington's disease, in Venezuela, developing a pedigree of over 18,000 individuals and collecting over 4,000 blood samples. This work helped lead to the identification of the Huntington's disease gene at the tip of human chromosome 4. These same blood samples have assisted in the mapping of other disease genes, including those responsible for familial Alzheimer's disease, kidney cancer, two kinds of neurofibromatosis, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease), dwarfism and others.
One result of this work was the development of a presymptomatic test which can determine who is carrying the fatal gene causing Huntington's disease prior to the onset of symptoms.
Dr. Wexler received an A.B. cum laude from Radcliffe in 1967 and a Ph.D. in clinical psychology from the University of Michigan in 1974.
Dr. Wexler currently holds or has held numerous public policy positions, including Chair of the Joint NIH/DOE Ethical, Legal and Social Issues Working Group of the National Center for Human Genome Research and the Department of Energy, Chair of the Human Genome Organization (HUGO), giving guidance during the Human Genome Project. She has served as a member of the board of directors of the American Association for the Advancement of Science on the Advisory Committee on Research on Women's Health, National Institutes of Health and as a Councilor, Society for Neuroscience. She is a Council Member of the Institute of Medicine, National Academy of Sciences. As their representative, she serves as a member of the Committee on Science, Engineering, and Public Policy (COSEPUP), National Academy of Sciences, National Academy of Engineering, and the Institute of Medicine.
Dr. Wexler is a Member of the American Academy of Arts and Sciences; a Member of the Institute of Medicine, National Academy of Sciences; a Fellow at the Royal College of Physicians, London, UK; a Fellow of the American Association for the Advancement of Science, Section on Neuroscience; and a Member of the European Academy of Sciences and Arts. She is an honorary Fellow of the New York Academy of Sciences.
Dr. Wexler has received numerous honors and awards, including several honorary doctorates. She received the Albert Lasker Public Service Award in 2003 and the Benjamin Franklin Medal in Life Science 2007.
In 2005, a biography entitled “Gene Hunter” was written about Nancy Wexler as part of a 10-volume Women's Adventures in Science series, co-published by National Academies Press and Scholastic Library Publishing. It is intended for junior high school kids – particularly to inspire young girls to go into the fields of math and science. There is also a website – www.iwaswondering.org – to accompany the book.
Carl Johnson, Executive Director for Science
Carl Johnson, Ph.D., is the Executive Director for Science of the Hereditary Disease Foundation. He is an accomplished chemist and model organism molecular geneticist. He has worked in the biotechnology industry for over 20 years.
He received his B.S. from the University of Chicago and Ph.D. from the California Institute of Technology for genetic and biochemical studies of the nervous system of the nematode (round worm) Caenorhabditis elegans.
Johnson did postdoctoral research at the University of Wisconsin and, in 1986, joined Cambridge Neuroscience, Inc. as Director of Genetics. In 1990, he and HDF Scientific Advisory Board member and Nobel Prize winner H. Robert Horvitz founded NemaPharm, Inc., the first functional genomics company focused exclusively on using animal models for human therapeutic discovery. NemaPharm was acquired by Sequana Therapeutics in 1997 and subsequently merged to form Axys Pharmaceuticals.
As Executive Director for Science, Johnson is responsible for the overarching scientific vision and activities of the Hereditary Disease Foundation. This includes managing all aspects of the scientific programs of the Hereditary Disease Foundation. He directs the three annual meetings of the Scientific Advisory Board, interacting with applicants to ensure that their proposals are the most relevant. He also follows up after funds are granted to maximize the usefulness of the research expenditures for the Hereditary Disease Foundation and the grantee.
Johnson organizes and moderates all of the Hereditary Disease Foundation's unique interdisciplinary workshops, focused on the most cutting-edge, scientific topics and questions. He also represents the Hereditary Disease Foundation in scientific interactions internationally.
Scientific Advisory Board
HDF has an unpaid Scientific Advisory Board (SAB) made up of 28 distinguished scientists from around the world – see attached list.
Former and current members of the HDF SAB include:
- winners of the Nobel Prize
- members of the National Academy of Science and its Institute of Medicine
- members of the American Association of Arts and Sciences
- winner of the President's National Medal of Science
- winner of the MacArthur Foundation “genius” prize
- director of the National Genome Research Institute, NIH
- director of the National Institute for Neurological Disorders and Stroke, NIH
- presidents of the Society for Neuroscience
- leaders in academia and the pharmaceutical industry worldwide
2. How are the HDF's Business Operations and Fundraising Efforts Structured?
- HDF is a 501(c)(3) nonprofit organization. Contributions to HDF are tax-deductible.
- HDF has annual audits and files its Form 990 in California and New York.
- HDF has a Board of Directors of 17 people who meet several times a year. There are an additional 44 Lifetime Directors. See attached list.
- Nancy Wexler serves as President of the Board.
- The Board of Directors Finance Committee reviews monthly and quarterly reports with the Controller.
HDF is a small, cost-efficient foundation with three full-time staff members:
- Carl Johnson, Ph.D., Executive Director for Science
- Karen Dean, Controller
- Julie Porter, Administrator
HDF's fundraising focus is on major gifts. HDF has been fortunate for nearly 40 years in finding dedicated longtime supporters, who have contributed a total of more than $70,000,000. Many of those people have been close friends and colleagues of the Wexler family and many of them became members of the Board of Directors. They have a passion for the mission of the HDF.
In addition, HDF's fundraising efforts include:
- Direct mail appeals
- Regional fundraising events – golf, cocktail parties, theme parties
- Gala – every two years
HDF does not have a full-time dedicated development department but outsources development components to professional staff with more than 20 years experience. This has proven to be more cost effective with an annual savings of about $100,000/year.
HDF keeps administrative and fundraising costs modest, averaging an expense ratio of about 85%. Of every dollar contributed to HDF, 85% is spent for “program” support, rather than general administration or fundraising.
3. How is the HDF Regarded in the Scientific Community?
HDF is considered an outstanding contributor to scientific research by the global scientific community.
Through grants, fellowships, fast-track contracts and the workshop program, the HDF continues to build a research community committed to the cure of Huntington's disease and related disorders.
Some examples of this recognition are:
The New York Times, The Wall Street Journal, Los Angeles Times, Sixty Minutes, Day One, and NOVA, among others, have all acknowledged the influence of the Hereditary Disease Foundation in pioneering new approaches in science and medicine.
Nancy Wexler has received a number of distinguished awards, including (most recently), the 2007 Benjamin Franklin Medal in Life Science from the Franklin Institute in Philadelphia. This award was given in recognition of her “vital role in the discovery of the gene responsible for Huntington's disease.” The description continues: “By leading combined efforts in human molecular genetics and neurosciences, Dr. Wexler established a model now used to investigate the genetic basis of inherited diseases.”
In receiving this award, Dr. Wexler joined such luminaries as Alexander Graham Bell, Marie Curie, Thomas Edison, Albert Einstein, Stephen Hawking, Jane Goodall, Gordon Moore, Jonas Salk and Frank Lloyd Wright.
At a Hereditary Disease Foundation gala on November 1, 2005, Dr. James D. Watson, Chancellor, Cold Springs Harbor Laboratory, Nobel laureate, 1962, recently offered some spontaneous remarks about the HDF:
“If one looks back in the development of human genetics in our current form, I think the Hereditary Disease Foundation played really the same role that the Rockefeller Foundation played in the 30s and 40s, when it permitted the development of molecular biology. It was a small group of people who weren't waiting around, but were giving money to the right people, with the thought that it was sensible.”
Francis Collins, M.D., Ph.D., Director, National Human Genome Research Institute, National Institutes of Health, and Recipient of the 2007 Presidential Medal of Freedom praised the Hereditary Disease Foundation Workshop Program:
“Everything I know about genomics I learned first at Hereditary Disease Foundation workshops!”
In the October 2000 issue of Nature Medicine, the Hereditary Disease Foundation was praised for its collaborative research efforts:
“Through the active recruitment of new ideas, new technologies and new researchers, the Hereditary Disease Foundation has set the stage for important progress in our understanding of HD pathology. Their commitment to collaboration and community building with the HD field serves as a model for all scientific groups tackling human diseases.”
4. How is the HDF Unique?
The Hereditary Disease Foundation created a new model for conducting research. In our competitive culture, scientists are pushed to work in isolation, pursuing insights independently. But many scientists prefer working collaboratively, especially when the problems are complex and challenging.
Workshops and Collaboration
The Hereditary Disease Foundation recognized this barrier. From its earliest days, Milton Wexler pioneered a unique program of workshops, bringing together international investigators from a wide variety of scientific specialties for focused discussions of research relevant to understanding Huntington's disease. Most investigators working on HD and related disorders have been recruited and their science shaped by the HDF's workshops
The HDF's workshops emphasize cutting-edge research and stimulate open discussion about research questions. Participants are urged to speculate, critique themselves and each other, and collaborate on critical insights and experiments.
A presentation by families with Huntington's disease begins each workshop. Family members teach the scientists something that no book or video can – that HD is a catastrophic concatenation of symptoms, affecting the entire family and its community. As a result, many scientists with no previous work in Huntington's disease develop a passion for finding a cure, speeding the pace and productivity of the push for answers.
Research and Collaboration
Scientific collaboration in the laboratory is a high priority for the Hereditary Disease Foundation. In larger projects which require many scientific lines of inquiry at once, HDF funded scientists work together toward the same end goal. Credit for breakthroughs is shared by all collaborators, regardless of which vein of research and scientist(s) “arrives first.” The HDF community understands that complex problems are solved more rapidly when cooperation between those with complementary skills takes place.
This model was used in 1993 when the Hereditary Disease Foundation organized The Huntington's Disease Collaborative Research Group to “capture” the Huntington's disease gene. All participants were equally credited for the discovery and were listed in the published paper as one author, The Huntington's Disease Collaborative Research Group. This single discovery of the Huntington's gene demonstrated for the first time to the scientific community that gene identification in human disease was possible; and in so doing, formed the backbone of the Human Genome Project, which identified all the approximately 20,000-25,000 genes in human DNA.
HDF scientists understand that only 1 out of 50 research projects is likely to produce big results, but all 50 conclusions are valuable to finding the ultimate answer(s). By collaborating, these scientists increase the likelihood of making a real contribution to humanity, even if their specific piece of a project leads to a dead end or is otherwise unglamorous.
5. What are the HDF Scientific Programs?
The Basic Research Grants Program and The John J. Wasmuth Postdoctoral Fellowships are focused on understanding the cellular and molecular causes of HD pathogenesis – with an eye to identifying approaches to therapeutic intervention.
The data generated with HDF funding often allow investigators to apply successfully for much larger, long-term funding from other funding agencies, mainly the National Institutes of Health.
HDF is also willing to take informed risks with early-stage research, giving purchase to many ideas that other funders would not consider.
- The Basic Research Grants Program: $50,000/year - supports projects that contribute to identifying and understanding the fundamental defects in Huntington's disease and related disorders. Grants are most often given for new, innovative ideas and technologies.
- The John J. Wasmuth Postdoctoral Fellowships: range from $40,500-56,000/year for a two-year period - are named in honor of the late John Jacob Wasmuth, an essential member of the Huntington's Disease Collaborative Research Group. The Hereditary Disease Foundation hopes that those granted fellowships bearing his name will seek John's level of imagination, rigor, creativity and spirit. Postdoctoral fellowships also serve to cultivate interest in HD research by bright young scientists, thereby building a new generation of researchers.
- Grants and Postdoctoral Fellowships are reviewed and selected by the Scientific Advisory Board.
- Over the past 3 years, about 33% of total program expenses went to Grants and 25% to Post-Doctoral Fellowships.
- Contracts: vary depending on project - Research funding is also provided through fast-track Contracts to pursue “translational research” projects, i.e., testing potential therapeutic interventions in mouse models of HD and, more generally, helping to move therapies from “bench to bedside.” These proposals are extensively shaped by the Executive Director for Science.
- Over the past three years, nearly 42% of program expenses went to these kinds of projects, including some focused on RNAi-based therapies, currently viewed as most promising.
The Hereditary Disease Foundation presents two special and prestigious awards annually. These awards cannot be applied for – the decision on the award recipients is made by the Scientific Advisory Board.
- The Milton Wexler Postdoctoral Fellowship Award is named after the founder of the Hereditary Disease Foundation. The Hereditary Disease Foundation restricts this annual award to research highly relevant to curing Huntington's disease.
- The Lieberman Award is presented annually to a worthy scientist, thanks to the generosity of Harry Lieberman, a trustee of the Hereditary Disease Foundation.
A list of funded Grants, Fellowships and Contracts is listed in the “Funding” section of the Hereditary Disease Foundation.
Partnering with Others
Nancy, Carl, and other members of their Scientific Advisory Board frequently lend their expertise to corporations and scientific groups around the world with the objective of sharing information so that all efforts to find a cure are as informed and effective as possible. HDF's chief goal is to fund the most promising research to cure HD without wasting time or effort.
For example, the Keep Memory Alive Foundation, which focuses on Alzheimer's disease, uses HDF as their scientific partner because of HDF's integrity and knowledge of how Huntington's research and other diseases are related.
In 2006, Nancy, Carl and HDF provided an intensive six-month consultation to the pharmaceutical company Novartis to help them shape their HD research program.
6. How Would my Money be Used?
In 100% of people with Huntington's disease, disease symptoms are caused by the expression of the abnormal HD gene. Accordingly, it is generally accepted that turning off the HD gene would be an effective treatment, even a cure, for HD.
RNA interference (RNAi) is a relatively newly discovered mechanism for turning down or “knocking down” the expression of any specific gene. Creating an RNAi-based treatment would be one of the most advanced therapeutic options for HD. (For more information about RNAi, go to http://www.ambion.com/catalog/workflows/siRNA/index.html.)
While a number of promising avenues of RNAi research are under way, HDF is concerned with making sure that multiple approaches are moved forward in parallel, in case the “primary” research veins already under way ultimately prove unsuccessful. It is these back-up research efforts that need funding.
7. How Does HDF Benefit Advancements in Other Disease Research?
The Hereditary Disease Foundation's primary focus is on finding treatments and cures for Huntington's disease, but some funded projects are known to also have a potential impact on other diseases.
There are ten other diseases with triple repeats; all are neurodegenerative diseases, but which gene is affected differs. Additionally, Parkinson's, Alzheimer's, and Lou Gehrig's disease (ALS) are neurodegenerative, but with the complication of mutations occurring in many genes.
For example, Parkinson's is caused by defects in one of 20 different genes, and so it is difficult to determine whether any one of the genes is responsible for the disease. Furthermore, only about 10% of Parkinson's is caused by known genes; 90% is “sporadic,” i.e. of unknown cause.
Alzheimer's is caused by defects in one of four genes, but again this accounts for only about 5% of cases, with the reminder being sporadic.
HD research contributes to the body of knowledge for all these diseases.
8. Why Give to HDF?
- We have conviction that your gift to HDF will be meaningful for the following reasons:
- The existence of Huntington's in the Wexler family creates a “personal passion” for finding the cure; their motives are impeccable; their focus, singular.
- HDF considers finding the cure for Huntington's disease urgent.
- HDF has demonstrated its commitment to finding a cure for HD for over 40 years.
- The depth of experience and talent of Nancy Wexler, Carl Johnson, and others on HDF's Scientific Advisory Board are acknowledged in the global scientific community.
- Current HDF funding targets RNAi research, which HDF considers the most promising route to finding a cure for Huntington's disease.
- HDF has identified other promising research in need of additional funds.
- Leverage! Not only is HDF's expense ratio low, making every dollar stretch, HDF scientists lend their expertise to others committed to this important work.
- HDF's organizational and scientific independence and collaborative research model have proven results.
- The benefits of this research are far-reaching and contribute to ending suffering associated with many diseases, at least one of which is likely to impact each of us personally during our lifetime.