What is genomic medicine?
Genomics is the study of an organism’s complete genetic code or DNA sequence, and how the genes made up by that DNA interact with each other and the environment to make that organism what it is. The human genome was sequenced for the first time with the completion of the Human Genome Project in 2003, but to this day the functions of many parts of the genome are not understood. Scientists are still working to improve our understanding of how exactly each person’s unique genetic code impacts their traits, their health, and their lives.
As genome sequencing technology improves, so does our understanding of the genome. The first human genome sequenced by the Human Genome Project cost $2.7 billion, while today anybody can purchase low-pass whole genome sequencing, a non-diagnostic version of whole genome sequencing, from Nebula Genomics for just $99. The combination of improved availability of sequencing and increased understanding of how genomic variation affects our traits has spurred the emergence of the field of genomic medicine: the application of an individual’s genomic information to help make personalized decisions about their medical care.
Because the availability of whole genome sequencing was fairly limited until recently and it takes significant time to translate cutting edge research into clinical practice, genomic medicine is still in its early stages. However, even today it is contributing significantly towards improved treatment outcomes, and this impact will increase by orders of magnitude in the next years as our ability to understand and analyze the genome continues to improve.
How genomics is transforming the practice of medicine today
While genomic medicine is still in its early stages, it has already had profound positive impacts on clinical diagnostics, treatments, and decision-making tools across many disciplines of medicine.
For some time now, we’ve had the ability to use genetic tests to diagnose simple genetic diseases such as cystic fibrosis, sickle-cell anemia, or Tay-Sachs disease. However, recent advances in genomic medicine have given us the ability to use genomic data to gain insight into an individual’s risk of developing conditions with more complex genetic components. A well-known example is that individuals with certain mutations in the tumor suppressing BRCA1 and/or BRCA2 genes are far more likely to develop breast cancer than individuals without these mutations. An individual who has undergone high coverage whole genome sequencing can determine whether or not they have a mutation in these genes. If they do, they can take action to lower their risk of breast cancer, such as taking certain preventative hormonal medications or getting regular breast screenings.
Another notable and relatively recent technique for predicting an individual’s risk of disease is the polygenic risk score. Polygenic risk scores sum the effects of an individual’s variations of many different genes to calculate a score that is predictive of the individual’s susceptibility to a disease. Scientists have been rapidly creating many new polygenic risk scores to predict susceptibility to many conditions. Some risk scores that are commonly reported in genetic tests today provide information on an individual’s risk of developing cardiac disease and type 2 diabetes in the future.
In addition to predicting disease risk and helping take preventative action, genomic medicine is already being used to administer personalized therapeutics to patients that are more effective than traditional therapeutics. One of the leading fields applying genomic medicine for this purpose is oncology. By sequencing samples from a patient’s tumor, physicians can recommend treatments based on which mutations the tumor possesses. Since these treatments target the tumor based on mutations that differentiate it from the normal cells in the body, they are usually significantly more effective and cause fewer side effects than traditional cancer treatments such as chemotherapy and radiation. A relatively well-known example of one such treatment is the class of cancer immunotherapy drugs known as checkpoint inhibitors, which are used to treat several different types of cancers. Several of these drugs work by targeting the protein PD-L1, which is encoded by the CD274 gene and helps cancer cells evade detection by the immune system. Therefore, by sequencing a tumor sample and checking whether or not the tumor expresses PD-L1 in a high proportion of its cells, we can gain insight into the chance that these drugs will be able to effectively treat that tumor. To emphasize how cutting edge the genomic medicine approach to oncology is, the FDA’s approval in 2017 of one checkpoint inhibitor, pembrolizumab, was the first time it approved a cancer drug based on tumor genetics rather than tissue type or tumor site.
However, this approach of tailoring treatments based on genetic profiles isn’t limited to tumors and oncology. The emerging field of pharmacogenomics, an application of genomic medicine, uses information about a person’s genome to help determine which drugs and treatments are best suited to their needs. Pharmacogenomics is currently gaining traction in psychiatry, as recent studies have suggested that an individual’s genetic profile can be used to determine which antidepressant and which antipsychotic drugs will be most effective for them.
One of the most cutting-edge advancements in genomic medicine is gene therapy, which is when a disorder is treated by inserting a gene into a patient’s cells or inactivating a mutated gene that is functioning improperly. A common method of doing this is by taking advantage of certain types of viruses that invade cells and inject their own DNA into the cell’s chromosomes. Scientists use modified viruses that inject useful genetic code instead of their own genetic material to fix genes that aren’t functioning properly. By doing this they can treat and sometimes cure genetic diseases. At this time only a handful of gene therapies are approved by the FDA for clinical use in the US for the treatment of conditions such as spinal muscular atrophy or retinal dystrophy. However, many new therapies are currently undergoing clinical trials.
The future of genomic medicine
Although it is a relatively new field, genomic medicine has already caused significant changes to many aspects of healthcare. However, as our ability to understand and analyze the genome improves over time, the impact of medical genomics will increase drastically.
The cost of whole genome sequencing has fallen exponentially and will continue to do so in the future until it becomes readily available at a price point that is affordable to everybody. As other issues that prevent people from getting sequenced such as privacy concerns are also addressed, there will be a significant upturn in people who are sequenced and an explosion of genomic data available to be used for research. With this data, researchers will be able to more rapidly improve our understanding of the human genome, greatly expanding the capabilities of genomic medicine.
Larger genomic data sets will allow researchers to gain an improved understanding of the degree to which many diseases and conditions are caused by an individual’s genetics and an improved ability to gauge individuals’ predispositions to various diseases based on their genomic information. An improved understanding of the genetics underlying specific conditions will also help provide insight into the cellular mechanisms underlying those conditions, which will give scientists new insights on how to develop cures. Because of this, individuals who have their genomes sequenced will be able to gain far more comprehensive, personalized insights into what diseases they are susceptible to and receive actionable information on preventative measures they can take regarding their lifestyle and environment to reduce their chances of ever experiencing these conditions.
Importantly, the genetic elements underlying more common conditions will also be better understood. For example, if your genome predisposes you to obesity, then your physician will inform you and give you personalized advice on lifestyle changes to help prevent you from becoming obese. Research has already begun on the genetics underlying many common conditions like heart disease and diabetes, but they are not yet well understood.
In particular, individuals with rare diseases stand to benefit from an increased availability of genomic sequencing. Since there are not many rare disease patients, it’s difficult for researchers to get access to enough data for studies on these diseases. Making genomic sequencing more affordable, appealing, and accessible for research will help researchers get the data they need to understand the genetics underlying these conditions and develop better diagnostics and therapeutics.
Additionally, the more widespread availability of genomic sequencing would enable us to greatly reduce or totally eliminate the prevalence of many genetic disorders with simple inheritance methods, such as cystic fibrosis or Tay-Sachs disease. If everybody is sequenced and aware of whether or not they are carriers for some of these disorders, they can take precautionary steps to ensure that their offspring do not inherit the conditions. For example, one option is using in vitro fertilization to ensure the condition isn’t passed down to their offspring. By eliminating or reducing the prevalence of these disorders, many people can be prevented from suffering and the healthcare system can be made more efficient.
Finally, as the mechanisms underlying genetic diseases are better understood and gene editing techniques like CRISPR-Cas9 are perfected, we will be able to use these techniques on a large scale to treat many genetic diseases. With gene editing, scientists will be able to treat or even cure genetic disorders by altering whatever genetic variants are causing them and restoring normal function. So long as germline cells (eggs and sperm) are not edited, these genetic changes should not be passed down to the offspring of treated individuals.
What consumers should know about personal genomics
It’s clear that the benefits of the advancement of genomic medicine will be great. However, there are concerns regarding genomics and privacy that anybody potentially considering participating in genomic medicine or research should be aware of. If you have your genome sequenced so that you can participate, you should be aware of who will have access to your data afterward. Many current direct to consumer genetic testing companies sell their users’ data to pharmaceutical companies. While we clearly believe that it’s beneficial to make more genomic data available to researchers, we also believe that your genomic data belongs to you, so you should have total control over exactly who gets access to your data. This is why the Nebula platform gives you the choice of whether or not to share your anonymized genomic data with researchers on a case-by-case basis and rewards you if you do choose to share it with them.
Additionally, depending on where you live, it could be possible for insurance companies to use your genomic data to set prices for you. In the United States, the Genetic Information Nondiscrimination Act of 2008 (GINA) prevents health insurance companies from discriminating against individuals based on their genetic data. However, other types of insurance companies such as life or disability could still use your data to set prices if they wish. At Nebula, we’re developing cryptographic techniques to ensure that only you and those you explicitly choose to share your data with can see it.
It’s worth noting that as genomic medicine advances, the privacy risks posed to individuals will grow as well. Scientists are already working on algorithms to let them generate an approximation of a person’s face using their genomic data. As these techniques advance in the future, it will be even easier for people to use your anonymized genomic data to identify you and gain very large amounts of information about you.
Ultimately, genomic medicine has the potential to make extraordinary positive changes to healthcare if more genomic data is made available to researchers, but we must carefully ensure that this data is used ethically and equitably. Our goal at Nebula is to enable you to be sequenced at an affordable price while maintaining ownership of your data and empower you to securely and anonymously share that data with researchers to help progress genomic medicine if you so choose.