We can expect the labels of many other drugs besides Camptosar to carry pharmacogenomic advice as research increasingly provides such knowledge. That research is delivering the knowledge is attested to by the growth in biotech patent applications in recent years. The application process itself has lengthened from about 12 months to more than 30 as a result of the growing volume. It is significant too that there are far more patents for specific genetic-related treatments than for genetic discoveries themselves (most of the 409,500+ US patents filed in 2005 — up from 344,717 in 2001 — were classified as “utility patents.”) Patents are no longer awarded just for discovery of the genetic sequencing for a protein; rather, what the protein does — its utility — must also be shown.

Nevertheless, the growth in patent filings for gene therapies is a reflection of our accelerating understanding of genetics-linked disorders including — in just the last few months of 2006 — the discoveries of a gene responsible for otitis media (“glue ear”) in children, a second gene associated with Crohn’s Disease, and a gene linked with autism. (The remaining sections in this issue expand on the list of discoveries and developments.)

Our understanding of human and disease genetics (and concomitant growth of patent applications) will accelerate further as major research projects such as the “ Cancer Genome Atlas ” (CGA), unfold. The goal of this US$1 billion+ project, announced in December 2005, is to map the molecular basis for cancers so they can be better diagnosed, treated, and prevented. US National Institutes of Health (NIH) director Elias Zerhouni called it “the beginning of a new era.” National Human Genome Research Institute (NHGRI) head Francis Collins commented: “The planets have aligned to tackle cancer in a comprehensive way that we’ve never had the tools to do before.” National Cancer Institute (NCI) head Andrew von Eschenbach put it most colorfully: “The future will look no more like the past than a butterfly resembles a caterpillar.”

There are reasons for their heady optimism: First, we have learned a lot — including the vital discovery that cancer is caused by errors in cellular DNA that can be identified and targeted with molecular medicines; and second, we now have technology capable of handling the mammoth complexity of mapping the cancer genome (and epigenome) at the molecular level.

Some of what we learned in 2006 resulted in a significant shift in our understanding of cancer, and therefore of research and clinical responses to it. Instead of concentrating on the organ in which a tumor appears, focus shifted more to the patient’s genetic makeup, finding the specific genetic changes driving an individual’s cancer, and targeting those changes with drugs. Examples include the lung cancer drugs Tarceva and Iressa, leukemia and sarcoma drug Gleevec, and breast cancer drug Herceptin, which work in certain patients with certain genetic makeup but not in others. New cancer subtypes were discovered in liver, brain, and prostate cancer patients, and in what NIH director Zerhouni called “groundbreaking” and “truly remarkable” research, scientists discovered nearly 200 cancer-causing genes, with 69 genes driving colorectal cancer and 122 fueling breast tumors. Each tumor analyzed was different; even tumors of the same organs had only about five genes in common, which could help explain why many chemotherapy drugs help only a fraction of patients. NHGRI director Collins commented that the new research could help doctors focus on the handful of genes, or possibly even the single gene, that would stop or kill a cancer, and thus help to better tailor therapies to patients.

In 2006 we also learned lessons about how groups of single-letter differences in DNA (called single-nucleotide polymorphisms or SNPs) tend to account for differences — including differences in disease predisposition — among groups of people. The HapMap project, an international follow-up to the Human Genome Project, has so far resulted in a partial catalog of genetic “haplotypes,” which should speed the search for the genetic roots of many common diseases. Knowing the haplotype has been estimated to translate into a 20-fold reduction in the cost of research into the genetic causes of disease. Indeed, the HapMap has already helped to identify a genetic defect that substantially increases the risk of age-related macular degeneration, and it is being used to identify genetic involvement in diabetes, Alzheimer’s disease, cancer, schizophrenia, asthma, high blood pressure, heart disease, and other medical conditions.

2006 also saw major progress in the drive toward a $1,000 individual human genome sequence, which will be vital toward finding genetic anomalies in individuals and in making personalized medicine (at least, diagnoses) financially accessible to nearly everyone. Solexa brought down the cost of sequencing an individual’s complete genome to $100,000 or less, and 454 Life Sciences’ latest machines are predicted to cut the cost to $10,000 within two years. VisiGen Biotechnologies has a five-to-10-year plan to sequence a person’s full genome within a day for $1,000.

In the meantime, research that will enable whole-genome sequencing to be usefully applied to patient care as soon as fast and inexpensive sequencers arrive in the doctor’s office was already underway in 2006, not only through large projects such as the CGA and HapMap but also through myriad smaller initiatives, such as a $5 million effort to built a database of DNA sampled from the blood of 400,000 patients at one academic medical center. This and similar initiatives around the world will supply data for pharmacogenomic research into adverse drug reactions.

Other significant research besides purely genetic analysis initiated in 2006 included a “pharmaco-metabonomic” method to predict how individual patients will respond to medicines. The method uses a combination of advanced chemical analysis of the body’s metabolism and mathematical modeling to predict responses to drugs. It may also help to diagnose diseases and predict an individual’s future illnesses.

Throughout the year, the array of techniques for undestanding genetic linkages to disease and the “biomarkers” that reveal their presence was already producing results for specific diseases, including those listed below (click on an item for the original Digest article about it):

• Parkinson’s Disease
• Autism
• Epilepsy/Autism
• Fibrodysplasia ossificans progressiva (FOP)
• Prostate cancer
• Colon, uterine, ovarian, and other cancers
• Age-related hearing loss
• Psycho-social predispositions
• Otitis Media
• Crohn’s Disease

This is an incomplete list, yet it still adds up to a stellar year in personalized medicine research. But that was not all: much of this and previous years’ research was already being translated in 2006 into personalized patient diagnoses and treatments, as the following sections document.