Rolling out the Red Carpet

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Thursday, July 17, 2008

Future of Genomics

Molecular biology has long held out the promise of transforming medicine from a matter of serendipity to a rational pursuit grounded in a fundamental understanding of the mechanisms of life. Molecular biology has begun to infiltrate the practice of medicine; genomics will hasten the advance. Within 50 years, we expect comprehensive genomics-based health care to be the norm. We will understand the molecular foundation of diseases, be able to prevent them in many cases and design accurate, individualized therapies for illnesses.

In the next decade, genetic tests will routinely predict individual susceptibility to disease. When the genome is completely open to us, such studies will reveal the roles of genes that individually contribute weakly to diseases but interact with other genes and with environmental influences, like diet, infection and prenatal exposures to affect health.

By 2010 to 2020, gene therapy should also become a common treatment, at least for a small set of conditions. Within 20 years, novel drugs will be available that derive from a detailed molecular understanding of common illnesses like diabetes and high blood pressure. The drugs will be designer therapies that target molecules logically and are therefore potent without significant side effects. Drugs like those for cancer will routinely be matched to a patient’s likely response, as predicted by molecular fingerprinting. Diagnoses of many conditions will be much more thorough and specific than now. For example, a patient who learns that he has high cholesterol will also know which genes are responsible, what effect the high cholesterol is likely to have, and what diet and pharmacologic measures will work best for him.

By 2050, many potential diseases will be cured at the molecular level before they arise, though large inequities worldwide in access to these advances will continue to stir tensions. When people become sick, gene therapies and drug therapies will home in on individual genes, as they exist in individual people, making for precise and customized medical treatment. The average life span will reach 90 to 95 years, and a detailed understanding of human aging genes will spur efforts to expand the maximum span of human life.

In Future, the complete DNA sequencing of more and more organisms, including humans, will revolutionize biology and medicine. It is predicted that genomics will answer many important questions, such as how organisms evolved, whether synthetic life will ever be possible, and how to treat a wide range of medical disorders.

If, within a few years, scientists can expect to amass a tidy directory of the gene products—RNA as well as proteins—essential for life, they may well be able to make a new organism from scratch by stringing DNA bases together into an invented genome coding for invented products. If this invented genome crafts a cell around itself and the cell reproduces reliably, the exercise would be the ultimate proof that we understand the basic mechanisms of life.

In the last 50 years, a single gene or a single protein often dominated a biologist’s research. In the next 50 years, researchers will shift to studying integrated functions among many genes, the web of interactions among gene pathways, and how outside influences affect the whole system.

Within 50 years, with all genes identified and all possible cellular interactions and reactions charted, pharmacologists are developing a drug or toxicologists trying to predict whether a substance is poisonous may well turn to computer models of cells to answer their questions.

Being able to model a single cell will be impressive, but to fully understand the life forms we are most familiar with, we’ll plainly have to consider additional levels of complexity. We will have to consider how genes and their products behave in place and time—that is, in different parts of the body and in a body that changes over a lifespan.

So far, developmental biologists have striven to find signals that are universally important in establishing an animal's body plan, the arrangement of its limbs and organs. In time, they will also describe the variations—in gene sequence, perhaps in gene regulation—that generate the striking diversity of forms among different species. By comparing species, we’ll learn how genetic circuits have been modified to carry out distinct programs, so that almost equivalent networks of genes fashion, for example, small furry legs in mice and arms with opposable digits in humans.

In 50 years, we will fill in many details about the history of life, though we may still not understand how the first self-replicating organism came about; we will learn when and how – by inventing, adopting, or adapting genes – various lineages acquired, for example, new sets of biochemical reactions and different body plans. The gene-based perspective of life will have taken hold so deeply among scientists that the basic unit they consider will likely no longer be an organism or a species, but a gene. They will chart which genes have traveled together for how long in which genomes.

Scientists will also address the question that has dogged people since Darwin’s day: What makes us human? What distinguishes us as a species? Undoubtedly, many other questions will arise over the next 50 years. As in any fertile scientific field, the data will fuel new hypotheses. Paradoxically, as it grows in importance, genomics may not even be a common concept in 50 years, as it radiates into many other fields and ultimately becomes absorbed as part of the infrastructure of all biomedicine.

Genetic information and technology will afford great opportunities to improve health and alleviate suffering. But any powerful technology comes with risks, and the more powerful the technology, the greater the risks. In the case of genetics, people of ill will today use genetic arguments to try to justify bigoted views about different racial and ethnic groups. How we will come to terms with the explosion of genetic information remains an open question.