by Carol A. Westbrook
No doubt you are wondering why I wanted to do this. The short answer — because I can.
When I started my research career in the early 1980's, scientists such as myself understood how valuable the human DNA sequence would be to medical research, but it seemed an unattainable dream. Yet in 1988 the Human Genome Program was begun, proposing obtain this sequence within 20 years. I was hooked. I was active in the Program, on advisory panels, on grant reviews, and on my own research, mapping cancer genes. Obtaining DNA sequence was painstakingly difficult, while interpreting and searching the resulting sequence was almost beyond the capability of the computers of the time. Nonetheless, in 2003, a composite DNA sequence of the human genome was completed, 5 years ahead of schedule. Shortly thereafter, two of the leading genome researchers, J. Craig Venter and James Watson, volunteered to have their own genome sequenced in their research labs, and Steve Jobs purportedly had his sequenced for $100,000.
I never imagined that in 2013, only 10 years later, sequencing and computational technology would improve so much so that an individual's genome could be sequenced quickly and (relatively) affordably. I could have my own genome sequenced! For a genomic scientist like myself, this was the equivalent of going to the moon.
I found a company, Illumina, which offered whole genome sequencing for medical diagnosis. I wrote to Illumina, “I have had over 25 years of experience in the Human Genome Program, and at this time would like to truly explore what I contributed to, these many years. I think the time is right to do this. I am able to interpret the results based on my previous experience in this field, and am comfortable with any results that might be found. So is my family. Realistically, I am 63 years old and healthy, so my risk of discovering a dangerous genetic condition is minimal.”
Illumina invited me to participate in their “Understand Your Genome Program,” where I and about 50 others “sequencees” would have our DNA sequenced and attend a daylong seminar on the interpretation and significance of our individual results. We would receive our personal sequence on an iPad at the seminar. This program is a combination of education, publicity, and “getting the message out,” and the sequencing is offered at half the commercial cost–and within my budget. So I submitted my credit card info and sent in my sample on November 12, 2013, 10 years and 7 months after the completion of the first human genome was announced.
I hadn't really thought much about the implications of knowing my personal genome sequence until that morning, when filled out the required paperwork to accompany with my sample. A doctor's signature was required to order the test — no problem, I'm an MD — and there was an optional signature for genetic counseling — I signed that, too, since I have clinical experience in that area. Next, my personal medical history: a checklist of common conditions that might have a genetic link (e.g. asthma, blood clots), and whether or not I was adopted. That was easy, I'm pretty healthy and I'm not adopted.
The family history took longer because my father and mother came from large families, 12 and 5 siblings, respectively, and I have 3 sibs of my own. Heart disease, high cholesterol and strokes run rampant in my dad's family. But I never really noted that there was cancer on my mother's side and I, too, might carry a predisposition, too. And Mom did develop Parkinson's disease, and eventually non-Alzheimer's dementia. Hmm. That was something to think about. Did I want to know?
Finally, the informed consent. I signed a statement agreeing to go ahead with the test, and acknowledging that I understand the implications and/or will discuss them with my doctor. I agreed to let them keep my leftover specimen for research. I was also asked to indicate whether there were any categories of genetic diseases that I might find that I did not want to know about, such as those that can't be treated, or progressive neurologic conditions like Huntington's disease, or genes that put me at risk for cancer. I decided that I wanted everything revealed. I signed the forms and sent in the sample.
The next step was to talk to my children and siblings (2 brothers and a sister) about my pending genome sequence, reminding that that they each have a 50-50 chance of carrying any gene that I have. I offered to let them to know my results, or to opt out for some or all of the genes, as I was asked to do. Everyone was okay with this because they knew I was healthy, I was past the age for many genetic conditions, and I didn't have cancer. My son jokingly said “sure, but don't tell me if I have Huntington's disease.”
Although I'm certain I don't have Huntington’s disease, I might still carry gene that puts me at risk of a disease, such as cancer or diabetes, but never develop the disease. Geneticists call this “low penetrance.” My children my get the gene and the disease. I might also carry a single gene for a recessive condition, such as hemochromatosis, which causes disease only if you inherit two abnormal genes. Who knows what is in the half of my parent's genome that I didn't inherit but my siblings may have? Or in my children’s' father's DNA? Finally, there are X-linked genes, in which women carry the gene and pass it on to their daughters, but only sons and grandsons develop the disease. Some examples are color blindness and hemophilia. Clearly there are results of my genome sequence that may impact my relatives. I decided to bring my daughter along with me to the March reveal, and to bring her iPad along.
At this time, my DNA is going through the sequencer and the results are being uploaded to the iPad. I am curious to know what I will find. There may be some data on ethnic origins, which may be helpful in understanding my heritage, as my father's father was illegitimately conceived shortly before his mother emigrated from Poland. Was my great grandfather Polish, or will we find genes from some far-away place? Of course, it will also be fun to know what percent of my genome is Neanderthal, too. And from the health perspective, I will be screened for the “known” genetic conditions, such as those revealed by the less inexpensive, more-limited chip-based DNA tests, such as 23andMe. This is valuable information, particularly as it might identify risk factors (cardiac, cancer, diabetes, etc.) or unexpected interactions with medications.
Learning about the known genes is useful but, in most cases, it is not going to make a major impact on a person's health. And, considering the expense, it is certainly not going to justify implementing whole genome sequencing as a standard part of our medical care — at least not for now. But most of the current discussion on the benefits of genome sequencing has been one-dimensional, focusing on the significance of identifying these known genes and risk factors. Yet what excites me about this project is not the known genes, but the incredible potential of a person's DNA sequence having a major impact on his health and longevity in the future, in ways that we cannot even predict.
Consider, for example, common conditions that clearly have a genetic component but can't be pinned to a single gene. These include asthma, rheumatoid arthritis, lupus, cancer, hypertension, diabetes, obesity, metabolic syndrome, kidney failure, anemia, cancer, depression, schizophrenia, obesity, heart attacks, osteoarthritis and many others. In fact, conditions like these probably cover the majority of all doctors' visits (excluding infection and accidents). These are the “unknown unknowns,” where combinations of genes and environmental factors come to play. Perhaps we will be able to use our genome sequence to prevent these diseases by targeting the mutation, or lessen the severity of the condition, or modify outside factors that impact them.
-What if you knew that would get diabetes if you were overweight, but you also knew that you could prevent this obesity by modifying a gene in your liver?
-What if you knew that your daughter had the potential to be a math genius? Would you help her develop her potential?
-What if your doctor could treat your hypertension with an individualized combination of drugs that had no side effects for you?
-What if you learned you have a risk of schizophrenia, but could prevent it by a treatment designed target the DNA sequence and stop its progression?
-What if you knew what biochemical subtype of depression you had, so you could treat it with the correct drug?
Impossible dreams? Sure, but so was obtaining the complete human genome sequence 1988. There is no question that genome research is moving so rapidly that we don't even have a vision of where it will be in 10 years. But I'm confident that the medical implications will strengthen as research continues and more complete genomes are compiled. I am pleased to be an early contributor. I will have my iPad at the ready when some of these new discoveries are made.