This documentary explores the promise and the challenges of the new age of personal genomics, from genetic surveys offered by direct-to-consumer companies like 23andMe to full genome sequencing. The documentary asks us to image how the world will be different once whole genome sequencing is available at $1000 or less and becomes routine. How will this shift the field of medicine from expensive treatment of end-stage disease to prevention? What are the current successes and failures? What are the ethical, legal, and social implications of widespread whole-genome sequencing?
We see whole-genome sequencing applied to a series of medical cases. Noah and Alexis Beery are twins. They were initially diagnosed with cerebral palsy, but actually turned out to have a two inherited disorders that are treatable with drugs, a result revealed by whole-genome sequencing. Joe Beery, their father, says that whole-genome sequencing saved their lives.
Andrew Schmitz, 5 years old, is not so lucky. He has had repeated viral infections, strokes, and brain surgery, yet despite whole-genome sequencing, scientists working with Dr. Howard Jacob are still looking for the responsible gene. Nicholas Volker, another of Jacob's young patients, is more fortunate: whole-genome sequencing revealed a novel mutation in XIAP. He was completely cured of an immune system disorder by a transplant.
We meet two cystic fibrosis patients. Michael McCarrick, 27, has severe lung damage. Paul Glynn, who is much younger, spends part of every fall in the hospital. Both have mutations that will respond to Kalydeco, a drug developed by Vertex Pharmaceuticals that restores the function of the protein defective in cystic fibrosis for patients with a specific allele. Michael McCarrick experiences some improvement, but his lungs are already too severely damaged, and he dies while awaiting a lung transplant. Paul Glynn improves enough to make the local football team.
We see progress in the biggest genetic disease of them all, cancer. Tom Garpestad, 50, was diagnosed with metastatic melanoma and given a month or two to live. Whole-genome sequencing of his tumors revealed that they carried a BRAF mutation, which made them highly responsive to an anti-BRAF drug which, unlike chemotherapy, had no side effects. His tumors shrank dramatically, but some returned. A second gene-specific drug has had limited success, but Tom is grateful for the eight months of normal life that he gained from the therapy.
The results of whole-genome sequencing are highly beneficial if they reveal a defect that is treatable. There is a list of about 200 "actionable genes." What about the others? We meet Katie Moser, a volunteer for the Huntington's Disease Society. Huntington's Disease is a dominant genetic disorder that produces symptoms of neurological degeneration, typically in the fifth decade. We see Katie Moser assisting Meghan Sullivan, who developed symptoms of Huntington's disease while a sophomore in college. Katie Moser has a family history of the disease, and wanted to be tested so that she could plan her life. She learned that she will eventually develop Huntington's disease. The knowledge has had repercussions: dates disappear, and she has family members who no longer speak to her, because they must now confront their own genetic status.
Journalist Catherine Elton raises the ethical problem of the burden of knowing. She was at risk for inheriting an allele of BRCA1 that would put her at high risk for developing breast and ovarian cancer, but at 27, did not want the knowledge to influence her life decisions. She refused genetic testing. She married and started a family, but developed breast cancer during her second pregnancy. She remains convinced that she did the right thing.
These stories are interlaced with experts in genomics explaining the basics of genetics, genomics, SNP typing, and whole-genome sequencing. Experts in bioethics raise important questions. We are asked to imagine a future four or five years from now where our tablet computers would display a easily-interpreted guide to our risks for many diseases, allowing us to engage in preventative medicine. We are also asked to imagine how our potential mates, employers, and insurance companies might use or misuse this information.
It is hard to imagine how a documentary of this length could possibly cover the essential material while remaining clear and interesting, but this film really delivers. The additional material presented on the website is a valuable addition for people who want to know more.
The biology content in this documentary is outstanding. We learn the basics of genomics from:
This documentary packs the basic biology into a remarkably short film. We learn that the genome is a big place, that DNA encodes proteins, that variations in DNA sequence causes changes in protein sequence that affect protein function and create disease states. We learn that altered proteins associated with disease states can be targeted by highly specific drugs.
Perhaps more importantly, we understand that this science is still in its infancy. The list of "actionable genes" is remarkably short (200 genes), but we also hear the point of view that any answer, including one that is not currently actionable, might represent progress. Several scientists acknowledge that the science is still in its infancy, but express great hope for the future.
Perhaps this is best illustrated by a conversation with Francis Collins, who knows the current state of genomic knowledge as well as anyone. Dr. Collins expressed reservations about the utility of personal genotyping, but submitted samples to three genotyping companies anyway. All three agreed Collins was at a substantially increased risk for getting type 2 diabetes. He began working out regularly and lost 27 pounds. For some other conditions, the three different companies disagreed on his risk level.
We also learn that genes interact with each other and with the environment. Several scientists caution us against genetic determinism. We see a clip from Gattaca in which a geneticist presents a couple with embryos derived from in vitro fertilization for their approval, with many undesirable traits screened out. Many of the traits are currently known to be complex, with many genes making small contributions and interacting with the environment. Eric Lander points out that one of the traits likely to be of interest to eugenicists is height, and that we know of about 180 genes affecting height, making embryo screening impractical.
It is not surprising that the biology here is all accurate, given the experts who are included in this film. What is remarkable is that they have succeeded in conveying the sense of exploration, uncertainty, and rigor that is the essence of science in so short a film.
The ELSI content is excellent. The key questions connected with genomic medicine are raised, and different points of view are presented. Some of the people that we hear from on ELSI issues are:
The film looks at many of the key ethical, legal, and social implications of genetic testing as it exists today and as it might exist in the world of the near future, when whole-genome sequencing is cheap and widely available.
Beginning in the current world, the implications of genetic testing for breast cancer risk are explored. Women who might have inherited risk alleles for BRCA1 or BRCA2 have the option of finding out their status. They will then be faced with the burden of knowing, which will affect their decisions about relationships and starting a family. People at risk for inheriting the dominant risk allele for Huntington's disease, or a predisposition for Alzheimer's or Parkinson's disease, can find out about their potential future, but without gaining the ability to do very much to prevent it. While some people would prefer to learn their status for such diseases in order to facilitate planning for later in life, people are part of families, and in some cases discovering one's own genetic status would change the odds of family members being affected.
There is an ongoing debate as to whether most people are capable of handling the level of information that they would obtain from whole-genome sequence. Will people over-interpret probabilistic statements and engage in unnecessary diagnostic procedures? Will people who are told they are not at elevated risk for heart disease or cancer gorge themselves on junk food and take up smoking?
Balanced against these negative outcomes, we see that whole-genome sequencing might offer a young person a lifetime program of preventative care based on their individual risk factors. In current cancer therapy, tumor genotyping can determine whether aggressive chemotherapy or gene-specific drugs are called for. For children with inherited life-threatening conditions, whole-genome sequencing, even with the current state of knowledge, might offer their only hope for treatment.
When whole-genome sequencing is cheap and widely available, how will it affect selecting mates or employees? If someone does not offer genomic data, can we lift their genome from a drinking glass that they have used and check them out anyway? Will potential employers skip over candidates at risk for expensive, disabling diseases in order to draw employees from a pool offering lower risk for health care costs?
The range of opinion offered on these subjects from carefully-chosen experts is outstanding.