I have wanted to learn more about the current status of personalized genomics for some time, and I was hoping the release of Dr. Francis Collins’ new book “The Language of Life” could help bring me up to speed. Dr. Collins is the current director of the NIH, and he was also the head of the Human Genome Project.
Overall, I like the book, and I think Dr. Collins does a good job presenting facts objectively, providing both optimistic and pessimistic evidence. However, readers should be careful to distinguish between “potential” applications and current applications of personalized medicine; the potential applications greatly outnumber the tools currently in widespread use.
I have included relatively brief summaries of the main applications of personalized medicine and some cool factoids that I gleaned from the book:
1) Personalized drug treatments - This is the aspect of personalized medicine that I find most exciting. Adverse drug reactions are the fifth leading cause of death in the United States (although some problems are due to human error, rather than genetic sensitivities). Dr. Collins discusses the current use of diagnostic tests to guide prescriptions for 6-MP (leukemia), Warfarin (blod clot/heart attack), Ziagen (HIV), and Herceptin (breast cancer). There are also several drug sensitivities that can be revealed using genetic tests (such as 23andMe), but such genetic testing is not currently standard practice. Many other potential applications of personalized drug treatments are discussed, and Dr. Collins also discusses the numerous drugs that have been developed after discovering the genetic basis for various diseases (using genetic/genomic tools).
2) Assessment of risk factors in your own genome – This is the topic of the book’s introduction. Dr. Collins discusses his own family history and his interpretation of genetic tests provided by 23andMe, deCODE, and Navigenics. He also provides a list of his positive results at the end of the book. Although exciting progress has been made in this area, I think these tests need to be more accurate. For example, the three tests were not even in agreement as to whether or not Dr. Collins should have either increased or decreased disposition to prostate cancer (the difference was due to which genetic variants were considered as part of the test). 23andMe also predicted Dr. Collins would have brown eyes, when in fact he had blue eyes. New genetic associations are constantly being published, and I think companies need to be conservative and only test for reproducible associations discovered by independent studies.
3) Assessing risk factors when planning children – This is certainly the most controversial aspect of personalized medicine. Although couples can get individual genomic tests and simply forgo having children (or staying together) if they are both carriers for a severe, recessive disease (like cystic fibrosis), a more aggressive and controversial route would be pre-implantation genetic analysis (PGD). PGD involves in vitro fertilization, conducting genetic tests on the fertilized embryos, and only implanting the embryos that are free from serious diseases. This technology is already in use, but it will obviously raise concerns for those who either believe that life begins at conception as well as those who fear a GATTACA-esque future of designer babies. In fact, Dr. Collins reports that 42% of PGD clinics would be willing to apply this procedure for sex selection, and a California lab currently advertises providing selection for eye and hair color. Dr. Collins proposes regulating which traits can or cannot be selected for during this process, and he also raises the point that defining every trait genetically (as presented in GATTACA) would be impossible because a number of traits are determined more by environment than genetics and the number of embryos needed to produce the right combination of desired traits would be enormous and impractical. I also think it is worth recalling the current accuracy of genetic tests (recall that Dr. Collins was supposed to have brown eyes when in fact he had blue eyes). I am generally not a fan of government regulation, but I do see how this thing can get out of hand and would at least advocate giving people the facts necessary to view these tests with a critical eye.
4) Gene therapy and stem cells – Although I wouldn’t usually consider this to be “personalized medicine”, these therapies are disused in depth in the final chapter of the book. Collins discusses case studies for gene therapy treating LCA (a disease that causes blindness) and X-linked SCID (“bubble boy”) patients. In an earlier chapter, Dr. Collins discusses a case study where stem cells (containing double mutants for CCR5) implanted in the bone marrow of a leukemia patient was able to confer resistance to HIV. Collins also discusses the use of iPS stem cells (engineered from normal cells, not embryonic stem cells) to cure sickle-cell anemia in mice, but he also notes potential complications (i.e. one of the four genes used to induce these cells is an oncogene, and may cause cancer in human patients). However, it is important to remember that case studies can sometimes provide atypically good results.
1) There is currently a free government website that allows people to record and analyze their family history. Dr. Collins describes this as currently “the single most important source of information about your future health”, and I personally think this would be a cool extra credit activity for high school students to see how they can apply genetics to real-world problems…that is assuming students can prove they have used the website without handing their medical history over to their biology teacher.
2) Free tools already exist that allow people to keep digital copies of their medical records, which can be rapidly accessed by designated health care providers. Two such tools are provided in the book: Google Health and Microsoft HealthVault
3) In addition to the discussion of Dr. Collin’s family history and genomic analysis, he also describes catching malaria and TB (on separate occasions) as a volunteer physician and a medical intern, respectively. Of course, he successfully recovered in both cases.
In conclusion, I think “The Language of Life” provides a good review of the progress of genomics in biomedical research, and I would especially recommend it to nonscientists who want to learn more genomic medicine.