Biology is now in the early stages of an historic transition to an information science, while also gaining the tools to reprogram the ancient information systems of life. Few of us go more than a few months without changing the software programs we use in our electronic devices, yet the 23,000 software programs inside our cells called genes have not changed appreciably in thousands of years (although recent research suggests that a few have changed as recently as a few hundred years ago).
Medicine used to be hit or miss. We would find something through "drug discovery" that performed an apparently useful function such as lowering blood pressure, but lacking effective models of how these interventions worked, many of these drugs turned out to be crude tools with unanticipated side effects. We are now beginning to understand biology as a set of information processes, and we’re developing realistic models and simulations of how the processes involved in disease and aging progress. Moreover, we are developing the tools to reprogram them.
RNA interference (RNAi), which science learned about only in the past several years, can turn specific genes off by blocking the messenger RNA those genes produce. Because viral diseases, cancer and many other types of illness depend on gene expression at some crucial point, RNAi heralds a breakthrough technology. One example of a gene that we would like to turn off is the fat insulin receptor gene, which tells fat cells to hold on to every calorie. When that gene was blocked in the fat cells of mice during a study at the Joslin Diabetes Center, those mice ate a lot but remained thin and healthy. They lived almost 20 percent longer, obtaining the benefit of caloric restriction without the food restriction.1
Innovative means of adding beneficial genes to patients’ bodies are starting to overcome the hurdles for gene therapy, which have often involved difficulties with placing the modified genetic information precisely within the genome. United Therapeutics, a company I advise, has developed a technique that modifies cells in vitro, verifies that the new genetic information has been properly inserted, replicates the modified cell millions of times and then injects the modified cells back into the bloodstream, where they embed themselves into the right tissues. In animals, this method has cured pulmonary hypertension, a fatal disease; it is now entering human trials.
We also have new means of activating and deactivating enzymes, the workhorses of biology. Pfizer’s compound Torcetrapib, for example, inhibits the enzyme that destroys high-density lipoprotein (HDL), the good cholesterol, and thereby allows HDL levels to soar. Phase II FDA trials showed that the drug was effective in halting atherosclerosis, the cause of most heart attacks. Pfizer is spending a record $1 billion on phase III trials.
Another important line of attack is to regrow our own cells, tissues and even whole organs, and to introduce them into our bodies without surgery. One major benefit of this "therapeutic cloning" technique will be the ability to create tissues and organs from versions of our own cells that have been made "younger" by correcting DNA errors and senescence-related changes (such as the shrinkage of the telomeres at the ends of chromosomes). Such capacities constitute the emerging field of rejuvenation medicine. For example, we will be able to create new heart cells from your skin-derived stem cells and introduce them into your system through the bloodstream. Over time, the new cells will replace your old ones, resulting in a rejuvenated heart that has your own (corrected) DNA.
Rational drug design has been around for 20 years, but it is only recently that we have had the requisite genetic data, information models and reprogramming tools to accomplish it. While almost all drugs on the market today were created by way of traditional drug discovery, most new drug development is applying these increasingly intelligent targeted therapies.
