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From 1990 to 2003, researchers around the world — including some in Alabama — completed the Human Genome Project (HGP), an international, government-funded effort to identify and map all the genes that are included in human DNA. While the groundbreaking project successfully identified the locations and functions of each human gene, it was just the beginning of genomic medicine, a way of customizing medical care to a person’s unique genetic makeup.
Since the completion of the HGP, researchers have continued to study how a person’s genes affect his or her health. A great deal of groundbreaking work in that area is happening here in Alabama, led by the team at Huntsville’s HudsonAlpha Institute for Biotechnology.
The HGP research showed that any two humans are identical in more than 99 percent of their genes. While humans have many more similarities with each other than differences, those slight variations in DNA can have a major impact on whether a person develops a particular disease, how he responds to an infection and which drugs are most effective, says Howard Jacob, Ph.D., HudsonAlpha’s executive vice president for medical genomics. At Hudson-Alpha, scientists have developed cutting-edge technology for DNA sequencing, the process of “reading somebody’s entire DNA, ” Jacob says.
“Lots of people read little pieces of DNA, but we read the entire genome, which gives us all the information that shows what makes that person that person, ” Jacob says. “Imagine building a house with a partial blueprint versus a full blueprint. By doing whole genome sequencing, we have all the information we may ever need to help in diagnosing or treating illnesses for that person.”
Whole genome sequencing is used in other places, but HudsonAlpha — with partners at the University of Alabama in Huntsville, the University of Alabama at Birmingham, the University of Alabama, the Auburn University School of Veterinary Medicine, the University of South Alabama’s Mitchell Cancer Institute and Children’s Hospital of Alabama — has developed technologies and methods for doing it for about the same costs as partial genome sequencing. And in Alabama, researchers and clinicians are using whole genome sequencing to make life-changing differences for current patients and the future of health care.
“For the first time in history, we are able to read nearly all the DNA bases that provide the blueprint of life, ” says Shawn Levy, Ph.D., faculty investigator and founding director of the Genomic Services Laboratory at HudsonAlpha. “Every single living thing is based on the same fundamental building blocks, and the variations in size and content on their genomes creates the diversity of life. We now have the ability to read and compare those genomes and to bring those capabilities to improve human health care.”
Economic Impact of Genomic Medicine
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Health care is big business, and the work happening at HudsonAlpha and its partner locations represents positive economic news for Alabama. HudsonAlpha-based scientists continue to discover new genetic markers associated with specific health conditions. For instance, researchers there discovered a new gene signature associated with triple negative breast cancer last year, which could lead to more targeted treatment for a devastating form of the disease.
But in addition to new genetic discoveries, HudsonAlpha has made strides in developing software that can process and decipher reams of genetic information, as well as hardware that can securely store and catalog loads of human genetic data. To that end, HudsonAlpha has assembled, in addition to genetic and clinical experts, a team of experts in accompanying fields, such as software development, informatics and information technology.
“When you sequence a genome, you derive a terabyte of information from each person, ” says Liz Worthey, Ph.D., faculty investigator and director of software development and informatics at HudsonAlpha. “The challenge is to take all that data and make it useful.”
Worthey and her team have developed software that takes that data, aligning billions of pieces of an individual’s genome with reference data, and identifying all the places where that person is different from the standard.
“Most people have about 6 billion variances in their DNA, but many of those variances aren’t associated with disease; they just determine things like hair color and eye color, ” Worthey says. The process of determining which variances could be associated with disease took about nine months, just a few years ago. Today, with the software Worthey has developed, the process takes about 90 minutes, and then the data is ready to be studied by a human expert.
Furthering its economic impact, HudsonAlpha also is helping to launch new startup companies such as Ploid Storage and Kailos Genetics, both of which are developing new technology to assist medical genomics and are located on the HudsonAlpha campus.
Health Impacts of Genomic Medicine
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For the scientists and physicians who work in Alabama’s groundbreaking genomic medicine industry, economic impacts take second place to the impact of their work on human health. For instance, David Bick, M.D., spent 13 years as a professor at the Medical College of Wisconsin, where he also led a pediatric genetics clinic and a genomics lab, becoming a nationally recognized leader in the field of genomic medicine. He and a group of colleagues left Wisconsin in 2015 to join the faculty of HudsonAlpha because they saw a great opportunity to use whole genomic sequencing to make a positive impact on the health of more patients.
“HudsonAlpha has the most advanced sequencing instrument available in the world, the HiSEQX, which was a remarkable resource for the group of us in Wisconsin, ” says Bick, who now serves as chief medical officer at HudsonAlpha and medical director of the Institute’s Smith Family Clinic for Genomic Medicine, which opened in 2015. “HudsonAlpha had the sequencing technology, and we brought the informatics and the clinical knowledge to apply to that sequencing.”
At the Smith Family Clinic, Bick and his team focus on using genome sequencing to diagnose diseases, especially in children, that have not been diagnosed through traditional avenues. Up to 10 percent of Americans have undiagnosed diseases, according to Jacob. Children may suffer from seizures, delayed development, intellectual disabilities or autism with no clear diagnosis.
“Some of the conditions are simply given names that are descriptions of the symptoms rather than a true diagnosis, ” says Greg Cooper, Ph.D., faculty investigator at HudsonAlpha. “We receive a blood draw, perform whole genome sequencing, and map out every single piece of the DNA. We look for genetic changes in those children that might underlie the symptoms they have.”
About a quarter of the time, Bick and his team find the answer, he says. While that means many patients remain undiagnosed, “new gene-disease connections are being discovered all the time, ” Bick says. “And once we have your genome, we continue to check against new research to find an answer. So if we don’t have a diagnosis this year, we may have one next year.”
As the whole genome sequencing center for the Undiagnosed Diseases Network, funded by the National Institutes of Health, HudsonAlpha receives cases from across the country. And HudsonAlpha has delivered diagnoses in more than 100 Alabama cases in the past few years, Levy says. For the families who receive concrete diagnoses, the sequencing work done here is life changing. While there may not be a cure for the genetic disease that is diagnosed, “there are strategies that can help, ” Cooper says. “Many people experience improved medical management once they have a correct diagnosis.”
For instance, one young patient suffered from undiagnosed symptoms for several years, until genome sequencing at HudsonAlpha resulted in a diagnosis of Rett syndrome. “Now she sees one of the world’s leading physicians for treating Rett syndrome, and her family would have never known that’s who she needed to see until she got a proper diagnosis, ” Cooper says.
In addition to helping achieve difficult diagnoses, genomic medicine has made great strides in pharmacogenomics, which is the analysis of key genes that dictate how a person metabolizes drugs. “Some people are, genetically, ultra-fast metabolizers of pain medication; therefore, they need to be given higher doses, ” Levy says. “And some people’s genetics prevent them from responding at all to common drugs.”
In fact, up to 18 percent of drugs being taken today are being taken by people who can’t process them correctly, Jacob says. In his own case, Jacob’s genetic assay shows that “there are 50 common drugs I can’t process correctly, ” he says.
Understanding how a person’s genetics affect his or her ability to process medicines can affect anesthesia and all types of treatments for various conditions. While a pharmacogenomics analysis, often referred to as PGX, is widely available for physician use, such tests are not yet widely used, Levy says. HudsonAlpha’s Smith Family Clinic now offers Insight Genome testing, which sequences the genomes of healthy people, allowing participants to learn about how (and whether) their body will respond to various drugs, and whether they are susceptible to contracting various genetic-related diseases. The Institute also adds each participant’s genome into its research program.
As the field of genetics continues to provide new knowledge and informed practice to the field of medicine, scientists and practitioners in Alabama remain on the cutting edge. And the people of Alabama, with access to the latest studies and care, will continue to benefit.
Nancy Mann Jackson and Dennis Keim are freelance contributors to Business Alabama. They are based in Huntsville.
TEXT By NANCY MANN JACKSON // Photos by dennis keim
