If all that you recall about genetics - the science of heredity - are Mendel's garden pea experiments or how to diagram your chances of having a brown- or blue-eyed baby, then you have a lot of catching up to do. And there's likely no better place on the planet to gain that education than in New Jersey, where some of the most advanced genetic research and gene-based therapy are being conducted.
As far back as 1953, groundbreaking genetic research was being conducted in Camden by Lewis Coriell, M.D., Ph.D. As founder of the first nonprofit academic medical research institute in South Jersey, now known as the Coriell Institute, and at a time when scientists could not grow human cells in culture without detrimental contamination, Dr. Coriell was a pioneer in growing healthy human tissue cultures. His work helped create the technology that made it possible to grow the cells used for polio virus research and develop and implement the polio vaccine.
Today, the Coriell Institute focuses on three primary areas: the emerging field of personalized (also referred to as predictive) medicine, stem cell research and biobanking.
"When the Human Genome Project to map the entirety of human genetic information began in the late 1990s, it took 13 years and cost some $3 billion to sequence a single genome," reports Michael Christman, Ph.D., Coriell's president and CEO. "Over the past half-dozen years, the required time and cost of determining an individual's genetic profile have come down significantly. Having this information is invaluable as it can help physicians better counsel patients and target and treat their diseases."
Personalized medicine draws upon a person's genomic information to tailor treatments and prescription drug dosing to optimize health outcomes. The Coriell Personalized Medicine Collaborative (CPMC) research project, involving about 8,000 volunteer participants, studies the usefulness of genetic risk and pharmacogenomics in clinical decision-making and healthcare management.
In a major alliance with the United States Air Force (USAF), the CPMC is providing cutting-edge healthcare for USAF beneficiaries around the world by reviewing and evaluating medical evidence regarding genomic associations.
"The Department of Defense has one of the largest and most progressive healthcare services in the US, and recognizes the tremendous value in personalized medicine," Christman states. "Our vision and their mission are very much aligned in this area. We anticipate achieving milestones over the course of our partnership that will significantly advance genome-informed medicine."
Coriell is building upon its history in cell biology through its induced pluripotent stem cell (iPS cell) research. iPS cell lines are powerful stem cells which can be made in a lab from skin or blood cells - instead of requiring the creation of an-embryo. They then can be "reprogrammed" to take on the characteristics of any other type of cell, providing a significant tool for studying genetic variations.
Screening drug candidates in a stem cell model also could result in medicines that are better targeted for individual patients, he adds. And the technology will likely result in effective drugs getting into the market faster, since potentially toxic drugs can be identified prior to clinical trials. Further, it promises to reduce research and development costs and, in turn, the cost to patients for their prescription drugs.
In 1964, the Institute was awarded its first of many contracts by the National Institutes of Health (NIH) to establish what has become the world's most diverse collection - also referred to as a biobank or biorepository - of cells and other biospecimens for the study of genetic, neurologic and age-related diseases. From its bank of tens of millions of living cells, collected over decades from more than 100,000 people, the Institute provides samples to researchers all over the world.
Christman notes, New Jersey is home to "two of the biggest and best biobanks in the world." The other is located at Rutgers University in Piscataway.
Considered the world's largest university-based biorepository, RUCDR Infinite Biologics (formerly known as the Rutgers University Cell and DNA Repository) provides biological sample processing, clinical analysis and data and storage services to hundreds of research laboratories around the world. With more than 12 million biosamples, representing about 400,000 individuals, RUCDR has served as the National Institute of Mental Health's (NIMH) and the National Institute on Drug Abuse's (NIDA) primary facility for genetic analysis on the relationship between genetics and mental disorders and drug abuse, respectively, since the biobank opened in 1998.
"We are learning that mental disorders - in most cases - are similar to physical disorders in that the causes are not only biological, but genetic," states Jay Tischfield, Ph.D., scientific director and CEO of RUCDR Infinite Biologics, and Duncan and Nancy MacMillan Distinguished Professor of Genetics at Rutgers.
This theory also helps to explain why some combat troops suffer post-traumatic stress disorder (PTSD), while others, in the same unit, do not, Tischfield notes. For the US Army STARRS (Study To Assess Risk and Resilience in Servicemembers) program, the RUCDR is conducting research on factors that would help protect soldiers' mental health and identify others that put their mental health at risk. And since 2012, RUCDR has been supporting the US Department of Veterans Affairs'Million Veteran Program, processing and genotyping DNA samples from US military veteran volunteers to build an extensive database of genetic, military exposure, lifestyle and health information to help better understand how genes affect health and illness and thereby improve healthcare for veterans.
Complementing RUCDR's mission is Rutgers' academic commitment to genetics research. When Tischfield became the first Department of Genetics chair in 1998, he established the Rutgers undergraduate Genetics major, one of the only such programs in the nation. In 2000, Rutgers Genetics Professor Linda Brzustowicz, M.D., became chair of the department, which is in the School of Arts and Sciences' Division of Life Sciences.
"Genetics is transforming medicine and impacting our lives by helping us better understand illness and its treatment," comments Dr. Brzustowicz. "Rutgers was at the forefront in the study of genetics, with various departments focusing on related scientific areas. We ultimately combined our aggregate strengths and expertise into the Department of Genetics."
A physician scientist with a patient-orientation, Dr. Brzustowicz studies the genetics of schizophrenia, autism and specific language impairment, a heritable neurodevelopmental disorder where language ability fails to develop normally, despite normal hearing, education and intelligence.
"We know from identical twin studies that disorders are not entirely genetic; there can be environmental influences," Brzustowicz says. "But people can have a physical susceptibility to them, so understanding genetics can be a powerful way of identifying the inherent risk factors, which may help identify environmental factors that we can more easily control."
New Jersey hospitals, like Hackensack University Medical Center (HUMC), are also solidly behind the ongoing effort of customizing treatment for cancer patients. Andre Goy, M.D., chairman and executive director of the John Theurer Cancer Center (JTCC) at HUMC, reports there are "profound and unprecedented changes occurring in oncology: from the huge number of novel therapies - more than 3,500 currently in the pipeline (mostly biological novel agents that target a specific cancer cell abnormality) - to the growing appreciation of the molecular diversity of cancer."
Cancer traditionally has been defined based on the organ of origin (example, stomach, lung, blood, etc.) and features found mostly under the microscope, Dr. Goy explains. "However, even within a cancer subtype, there are dramatic differences among patients (i.e. cells are "wired" differently, which explains the differences in cancer cell behavior and patient outcomes). Thanks to the progress with whole genome sequencing and technology that allows much faster testing, it becomes clear that even with, for example, aggressive lymphoma, there are up to more than 12,000 distinct abnormalities or mutations between cases."
John Theurer Cancer Center's tissue repository was established seven years ago, collecting tumors and blood samples to help further the Center's "precision" or "tailored medicine" approach. Additionally, JTCC has a strong tradition of clinical research, with more than 250 clinical trials opened for enrollment between JTCC and its growing network RCCA (Regional Cancer Care Associates). A number of those trials already are looking at biomarkers to predict patients' responses and outcome and guide treatment recommendations, Dr. Goy reports.
In Camden, the MD Anderson Cancer Center at Cooper, a partnership between Camden's Cooper University Health Care and Houston'sMD Anderson Cancer Center, one of the country's premier cancer treatment and research facilities, opened in October 2013. Through this venture, MD Anderson's first in the Northeast, patients in Southern New Jersey have access to genetic counseling and testing to help them, especially those with family histories of cancer, determine and manage their risk of developing the disease.
"The study of genetics is the basis for the biotechnology industry, which has grown and continues to grow significantly in New Jersey," notes Debbie Hart, president and CEO of BioNJ, New Jersey's premier association of biotechnology firms. "Biology seeks to understand how cells function - what they do and how they do it. Biotechnology, the use of cellular and biomolecular processes, uses that knowledge to solve problems and make useful products."
Leading New Jersey biotechnology firms are utilizing genetic-based research and treatment protocols to address niche areas of healthcare and drug development. Among them, PTC Therapeutics, Inc. (PTC), South Plainfield, is recognized for its discovery and development of orally administered, proprietary small-molecule drugs that target post-transcriptional control processes - processes that regulate the rate and timing of protein production (protein is key to healthy cell development) and are essential to proper cellular function.
PTC's lead product candidate, ataluren, is used to treat patients with genetic disorders that arise from a "nonsense mutation," a genetic variance in a DNA sequence that results in a shorter, unfinished protein product. Ataluren is in late stage clinical development for the treatment of Duchenne muscular dystrophy and cystic fibrosis, both caused by nonsense mutations.
In research for another "orphan," or rare and currently incurable disease - spinal muscular atrophy (SMA), PTC last August announced the selection of a potential new treatment candidate in its SMA collaboration with Roche and the SMA Foundation.
"Genetic research has been the basis of all our work at PTC since our founding in 1998," states PTC President Claudia Hirawat. "Since we specifically target diseases caused by genetic mutations, we have to understand exactly where the mutations exist in order to develop appropriate therapies."
Further spurring PTC's research today is that patient genotyping has become almost commonplace and patients are conversant about their disorders, Hirawat reports. "Genotyping is a vital component in the diagnostic process - and patients know what mutation they have and where it is in the gene. Patient registries also enable us to reach out to physicians and viable candidates to participate in clinical trials."
Cancer Genetics, Inc. (CGI), Rutherford, develops and commercializes proprietary genomic tests and services to improve and personalize the diagnosis, prognosis and treatment of difficult-to-diagnose cancers, including hematological, urogenital and HPV-associated cancers.
Last November, CGI announced the first projects in its partnership with the Mayo Clinic. Named Oncospire Genomics, the joint venture will use the most advanced technologies available to speed the genetic testing of complex diseases and provide clinically relevant and actionable insights in critical areas of oncology. Initially, Oncospire plans to develop latest state-of-the-art diagnostic tests for lung cancer, multiple myeloma and follicular lymphoma, the second most common lymphoma in the US.
"With all the hospitals, universities, pharmaceutical, biotech and diagnostic companies in New Jersey, there is a lot of good research talent here notes CGI President and CEO Panna Sharma. "However, both the research and commercial components are essential to building successful companies."
He adds a major CGI goal is to develop products and services that will facilitate bringing genetic testing to the community hospital setting, so clinicians can serve their patients faster and better.
"It's now widely recognized that most chronic human diseases have complex origins involving diverse genetic factors that interplay with environmental components," says Tischfield. "It also has become clear that understanding the origins of complex diseases requires a novel, multidisciplinary mindset as well as new tools. There's little doubt that those of us involved in genetic research and treatment in New Jersey are leading worldwide efforts to provide treatments and cures that offer the greatest opportunities for improving human welfare."