Genome Sweet Genome

June 2000's announcement that the human genome had been mapped out well ahead of schedule merited the full lunar landing treatment. Nevertheless, at least one commentator reminded us that we haven't been back on the moon in more than 30 years, much less put it to practical use. An historic breakthrough yes, but we are talking in terms of decades before we start reaping the real benefits of our genomic knowledge.

According to Dr Francis Collins, head of the Human Genome Project of the NIH, writing in the New York Times, by the year 2010 genetic tests will help identify people at highest risk of particular diseases. By 2020, doctors will rely on individual genetic variations in prescribing drugs, and by 2030, clinical trials based on genomic information will be underway to extend the human lifespan. Thanks to our advanced knowledge, many experiments done on lab animals or humans can be completed on computers. By 2040, gene therapy and gene-based drugs will be available for most diseases, and the average life span will be 90 (the year this writer turns 91, to bring this down to a personal level).

One research scientist told this writer that Dr Collins may be painting an overly rosy picture in order to keep the funds flowing in. That may well be the case, but one should never discount the possibility of the unforeseen breakthrough, either.

Genes are responsible for making proteins, which are the working parts of human cells, serving a variety of purposes from acting as cellular ceiling joists to catalyzing chemical reactions. In the words of an article in the NY Times: "Understanding the role of every human protein - proteomics - will be one of the goals of the post-genome era."

But don't expect a Eureka! being cried out in some dark lab late at night over the discovery of a depression or bipolar gene. In all likelihood, mental illness stems not from a single gene, but from multiple genes acting with one another as well as reacting to environmental stressors.

Perhaps some of you recall the announcement made in 1987 by a group of scientists who were convinced they had found the bipolar gene. After an investigation of Amish families, they thought they had pinpointed the culprit near the tip of the short arm of chromosome 11, only to concede defeat two years later.

How naive we were.

Now, armed with the human genome, plus new technologies and insights, researchers are tracking how thousands of genes work together, as well as pinpointing suspect genes to specific chromosomal regions. Teasing out the mood genes remains a laborious process, but breakthrough findingss are starting to come in from researchers who are looking for genes that switch on certain brain functions rather than elusive genes specifically identified with a disease type - everything from how too much dopamine may cause psychotic episodes to how a genetic malfunction sets off the fear response to how that same genetic malfunction makes certain people vulnerable to stress to how certain gene mutations may result in individual cells failing to properly convert food to energy.

In 2000, gene therapists gave us a taste of tomorrow with the following two developments:

French doctors successfully treated three infants suffering from a disease that shuts down children's immune systems and forces them to live in airtight bubbles. In what is being hailed as a milestone of gene therapy, doctors removed bone marrow from the infants, isolated stem cells from the marrow, grew the cells in a lab, treated the cells with a virus that carried the gene for a missing protein, and returned the cells to the infants' bodies. These cells multiplied in the boys' bodies, outproducing the cells with the defective gene. The children have fully functioning immune systems, and two have lived normal lives for at least a year.
Researchers at the University of California, San Diego were able to restore deteriorating nerve connections in the brains of monkeys by transplanting brain cells genetically programmed to release a protein called "nerve growth factor." In 2001, doctors at the University of California, San Diego performed the first-ever surgical gene therapy on the brain of an Alzheimer’s patient. The 11-hour procedure involved implanting the patient’s skin cells, which were genetically-engineered to produce nerve growth factor, recently discovered to restore connections between brain cells. The quantity of implanted cells amounted to one hundredth of a teaspoon.

Meanwhile, at Stanford University, Robert Sapolosky PhD is experimenting with transplanting genetically-engineered material into the brains of lab animals, with a view to blunting stress response and enhancing brain cell recovery, two factors vitally linked to mood (see article). The task may well turn out to be Mission Impossible. Then again, a free trip to Stockholm is waiting if he succeeds. Säker färd.

For three free online issues of McMan's Depression and Bipolar Weekly, email me and put "Sample" in the heading and your email address in the body.

Updated June 13, 2004.

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