ADVERTISEMENT

Reprogramming Biology

Tinkering with our genetic programs will extend longevity
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.

Implants being developed at the University of Rochester and Boston-based StemCapture, Inc., imitate the mechanisms used by stem cells in trolling the vascular endothelium for damage signals, which indicate a need for repair. Molecules key to this trolling mechanism are coated onto the device to capture stem cells out of the bloodstream. DNA or RNAi molecules can also be sprinkled on this molecular coating to correct genetic errors and senescence-related changes in the captured stem cells.2

Nanotechnology can go beyond the limitations of biology. Harvard University and Massachusetts Institute of Technology researchers have designed nanoparticles with aptamers, genetic chunks that recognize the surface molecules on cancer cells. These nanoparticles can latch onto a cancer cell, burrow inside and release toxins to destroy it.3

Another scientist cured type I diabetes in rats with a nanoengineered device containing seven-nanometer pores that controllably release insulin while blocking antibodies. There are hundreds of other such examples.

Our ability to understand and even reprogram the brain, although in early stages, is also accelerating. We are doubling the spatial resolution of voxels (3D volumes) in brain scanning each year. The latest generation of in-vivo scanners can image individual interneuronal connections firing in real time. Effective simulations of about two dozen brain regions have been demonstrated, and IBM has begun an ambitious effort to simulate a substantial portion of the cerebral cortex at a detailed level.4

Rising numbers of artificial neural implants can replace diseased tissue, such as an FDA- approved implant for Parkinson's patients, the latest generation of which allows the patient to download software updates from outside the body.5,6

Now that biology is becoming an information technology, it is subject to what I call the "law of accelerating returns." Information technologies, including biological ones, double their price performance and capacity in less than a year. Sequencing DNA, for example, has come down in price by half annually, from $10 per base pair in 1990 to under a penny today.7 The amount of genetic data we have sequenced has more than doubled every year. It took us 15 years to sequence HIV, but we sequenced the SARS virus in only 31 days. This rate of doubling means that we will increase the capability of these technologies by a factor of 1,000 in less than a decade and by a billion in 25 years.

Human life expectancy was only 37 years in 1800.8 Such technologies as sanitation, antibiotics, and other medical advances have more than doubled it in 200 years. Our ability to reprogram the information processes of biology will dramatically increase it again, but this progression will be much faster because of the inherent acceleration of information technology. I expect that within 15 years, we'll be adding more than a year each year to remaining life expectancy. So my advice is: take care of yourself the old- fashioned way for a while longer and you may get to experience the remarkable century ahead.

1Flier SN, Kulkarni RN & Kahn CR. 2001. Proc. Nat. Acad. Sci. USA., 98:7475-7480.

2King, M.R., and Hammer, D.A. 2001. Multiparticle Adhesive Dynamics. Interactions between stably rolling cells. Biophys. J. 81:799-813.

3Farokhzad, O.C. et al. 2006. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Nat. Acad. Sci. 103: 6315-6320 http://www.pnas.org/cgi/content/abstract/103/16/6315.

4Graham-Rowe, D. Mission to build a simulated brain begins. 2005. NewScientist.com News Service. http://www.newscientist.com/article.ns?id=dn7470.

5Berger TW, et at. 2005. Restoring lost cognitive function. IEEE Eng Med Biol Mag. 24(5):30-44. http://cogsci.ucsd.edu/~desa/200/2005_09_EMBS.pdf.

6Abbott, A. 2002. Brain Implants Show Promise Against Obsessive Disorder. Nature. 419: 658.

7Carlson, R. The Pace and Proliferation of Biological Technologies. 2003. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science Volume 1 Number 3. http://www.kurzweilai.net/meme/frame.html?main=/articles/art0614.html.

7Oeppen, J and Vaupel, J.W. 2002. Broken Limits to Life Expectancy. Science 296.5570,1029-3.

Share this Article:

Comments

You must sign in or register as a ScientificAmerican.com member to submit a comment.
Scientific American Holiday Sale

Give a Gift &
Get a Gift - Free!

Give a 1 year subscription as low as $14.99

Subscribe Now! >

X

Email this Article

X