The Human Genome Project began in 1990. The goal of this research effort was to map and sequence the three billion deoxyribonucleic acid (DNA) base pairs and estimated 22,000 genes that make up the human genome—the biological building blocks of human life. Researchers completed the project in April 2003, under budget and more than two years ahead of schedule. The National Institutes of Health and the U.S. Department of Energy coordinated the research efforts of universities across the United States, along with those of international partners. Their work resulted in a high-quality map of the human genome that is now freely available in public databases.
Completed at a cost of $3 billion, their efforts also accelerated development of tools and technology for fast and inexpensive gene analysis. Over the past decade, the cost of gene sequencing has plummeted. Today, if you’re interested, you can get your genes sequenced for about $100. This combination of inexpensive access to large amounts of genetic data and researchers’ growing understanding about how genes work has unleashed a genomic revolution. This revolution will have a major impact in the fields of medicine, biotechnology, and the life sciences.
Nearly every human ailment has some basis in our genes. Yet, until recently, doctors were only able to take genetics into consideration for a limited set of diseases. Sickle cell anemia is one example. It has a simple, predictable inheritance pattern caused by a single gene change. However, the treasure trove of data generated by the Human Genome Project and subsequent research has enabled more powerful approaches. Scientists are now unlocking the role that multiple genetic factors—acting together and affected by the environment—play in complex diseases. Cancer and Alzheimer’s disease are two prominent examples.
The Fight Against Cancer
The genomic revolution will be a game changer in the fight against cancer. So far, major advances have come primarily in the form of better diagnostics. A recent New York Times article pointed to a Silicon Valley start-up preparing to offer genetic screening for breast and ovarian cancer so inexpensive that most women would have access to it. Color Genomics plans to charge $249 for an analysis of BRCA1 and BRCA2, the two main breast cancer genes, plus another 17 genes with known cancer risks. While no preventive treatment exists for women with the BRCA mutations, those who test positive can remain alert to the risk and catch potential new tumors as quickly as possible.
It is impossible to write about genetic testing and breast cancer without mentioning actor and director Angelina Jolie. Two years ago, Jolie discovered she had an 87 percent lifetime risk of developing breast cancer and a 50 percent lifetime risk of developing ovarian cancer. She made news when she announced she had a double mastectomy and her ovaries removed as a preventive measure after testing positive for the BRCA mutation.
But the BRCA mutation is just one example. Cancer, as we know it today, is a family of diseases characterized by the uncontrolled growth and spread of abnormal cells. Each of the more than 400 diseases in this family has a unique genetic signature, a specific set of mutated genes within its DNA. One of the newest developments in cancer detection and monitoring is called liquid biopsy. It’s a blood test that can detect and identify a cancer by matching DNA fragments circulating in the blood to the genetic signatures of a growing library of known cancers.
The capacity to identify cancers this way will have benefits beyond improved diagnostics. It will lead to more targeted treatment. Take the example of prostate cancer. It is difficult for doctors to know which tumors are likely to spread and which are not likely to pose a threat. “As a result, we tend to treat all prostate cancers as if they’re of the most ferocious variety,” according to Edward J. Benz, Jr., MD, president of the Dana-Farber Cancer Institute. “By understanding which genes brand a tumor as especially aggressive, we’ll be able to provide not only the right treatment, but the right degree of treatment, and at the right time.”1
An Interesting Approach to Alzheimer’s
Alzheimer’s is another complex disease and a looming health problem. The disease currently affects 5.4 million Americans at an annual cost of $200 billion.2 And with leading-edge baby boomers in their late 60s, those costs will rise, putting pressure on families, the healthcare system, and Medicare. Unchecked, prevalence of Alzheimer’s will quadruple by 2050.3 According to the website of Raleigh-based Muses Labs, “Alzheimer’s disease is fatal, and currently there is no cure or even a treatment that significantly slows progression of the disease.”
As Muses Labs’ Chief Technology Officer Dr. John Q. Walker explained, “there are dozens of factors that contribute to cognitive decline with age, but your genes can amplify or reduce the effect of these factors.” In fact, there is “one gene that swamps all others.” The E4 variant of the ApoE gene is the strongest genetic risk factor for Alzheimer’s disease. The ApoE gene encodes the protein apolipoprotein E. While our understanding of this protein’s role in Alzheimer’s development is evolving, 90 percent of people with two copies of E4 and 30 percent of those with one copy of the gene today are likely to develop the disease. That amounts to 27 percent of the U.S. population—or 75 million people—inclined toward Alzheimer’s based upon this single gene pair.
Drugs have not fared well as a way to deal with Alzheimer’s disease. According to Walker, “Over the past 10 years, of the 244 drugs that have gone through trials, 243 of them failed, and the one that got approved treats the symptoms and makes the condition worse.” The research of the Muses Labs team suggests that no simple cure for a disease like Alzheimer’s exists. Because it is complex biologically, “its treatment calls for a complex combination therapy that addresses many factors at the same time.” Muses Labs’ approach includes personalized therapies that combine drugs, diet, exercise, and other lifestyle aspects, which they think are the best way to reduce the inflammation and system imbalances at the root cause of Alzheimer’s.
Genetics and Environmental Factors
Information from the Human Genome Project is leading scientists to re-examine the role of genetics and environmental risk factors in the development of disease. They are drawing some interesting new conclusions.
Virtually all diseases result from the interaction of genetic variations with environmental risk factors such as infectious, chemical, physical, nutritional, and behavioral factors. They are finding that genetic variations do not cause disease. Rather, they influence a person’s susceptibility to environmental factors, creating a higher risk for certain diseases. This concept also explains why the same environmental factors affect individuals differently. For example, how a health-conscious 40-year-old has a heart attack, while others seem immune to heart disease, in spite of smoking, poor diet, and obesity. Genetic variations account, at least in part, for this differing response to the same factors.
While Angelina Jolie’s case is rare and somewhat controversial, it points out a recurring theme. Genetic testing can identify a potential susceptibility to a particular disease. From there, one can take action to track the issue, make preventive changes or, as she did, take preemptive action.
It seems that the biggest implication of the genomic revolution may not be treating or curing complex diseases like cancer and Alzheimer’s. It may be avoiding them altogether—or at least delaying their onset. As Muses Labs’ John Q. Walker said about the ApoE gene and Alzheimer’s disease, “if you have one E4, you need to pay attention and if you have two E4s, you really need to pay attention.” In his view, armed with genetic self-knowledge and the right therapy, few need suffer from Alzheimer’s in the future.
There’s a Downside, Too
Genetic testing has the potential to transform the way we manage health in ways that could lead to longer, healthier lives. Unfortunately, we must also consider the downsides:
- Misinterpretation of genetic information. The presence of a genetic variation, in most cases, indicates a susceptibility to a disease, not its presence. Some diseases are more influenced by genetic factors than others. This is called heritability. Meaningful interpretation of test results requires specialized skills and knowledge. Moreover, patients must know enough to make informed decisions.
- Workplace genetic screening run amok. Advocates suggest that screening job candidates for susceptibility to workplace risk factors, such as radiation or chemicals, could preempt potential health issues and their costs. While that seems prudent, it’s easy to imagine how reasonable workplace screening could go too far. Critics fear employers could use the same information improperly. For example, they could screen for susceptibility to chronic health issues as a way to reduce healthcare costs or cut down on absenteeism. In recognition of the potential for genetic discrimination, President George W. Bush signed the Genetic Information Non-Discrimination Act (GINA) into law in May 2008. GINA prohibits discrimination against a person on the basis of genetics for health insurance and employment.
- Insurance discrimination. While GINA prohibits genetic discrimination against a person for health insurance purposes, it does not cover life, disability, or long-term care insurance. Insurers can deny policies for the people most likely to need insurance based upon their genetics. This is especially troubling given a recent Harvard Medical School study that found that people who discover they have the E4 variant of the ApoE gene are five times more likely than the average person to buy long-term-care insurance.4
Given the newness of the genomic revolution, it shouldn’t be a surprise that unresolved social, ethical, and legal issues exist. GINA, for example, is an essential first step in the fight against genetic discrimination and misuse of medical information. But it is not perfect. Technological advances seem to have a way of outstripping norms and, over time, leading to a new normal (with a little controversy along the way).
Researchers have made dramatic advances in the decade since the Human Genome Project completed its Herculean task. Fueled by inexpensive gene sequencing and powered by big data, they are making rapid progress toward a better understanding of major health problems. While they have not yet identified many of the genetic risk factors for diseases, and the interaction of genes with other genes and genes with environmental risk factors needs further exploration, it is clear that the genomic revolution has begun.
In a 2011 TED Talk, Richard Resnick, Chief Executive Officer of GenomeQuest and former researcher on the Human Genome Project, said, “The prospect of using the genome as a universal diagnostic is upon us today … And what it means for all of us is that everybody in this room could live an extra five, 10, 20 years just because of this one thing.” If he is correct, despite the fact that we face many unanswered questions, we are likely to witness some amazing things in our longer and healthier lifetimes.
1 Benz, Jr., MD, Edward J. “Genomics and the Future of Cancer Treatment.” Stand Up to Cancer. Entertainment Industry Foundation (EIF). Accessed April 2015. http://www.standup2cancer.org/article_archive/view/genomics_and_the_future_of_cancer_treatment.
2 Alzheimer’s Association. “2013 Alzheimer’s Disease Facts and Figures: Alzheimer’s & Dementia, Volume 9, Issue 2.” Alzheimer’s Association. Alzheimer’s Association. Last modified 2013. Accessed April 2015. https://www.alz.org/downloads/facts_figures_2013.pdf.
3 Reynolds, Chandra A. “Alzheimer Disease: Genetic and Environmental Influences.” University of California, California, USA, January 2013. Accessed April 2015. doi:10.1002/9780470015902.a0005243.pub2.
4 “It’s Legal For Some Insurers To Discriminate Based On Genes.” Narrated by David Schultz. All Things Considered. NPR, January 17, 2013. http://www.npr.org/sections/health-shots/2013/01/17/169634045/some-types-of-insurance-can-discriminate-based-on-genes.