In the Zone, Part 2

AN AGE OF CONTROL: We live in a new age, a time Sir Ian Wilmut calls the "age of biological control," where he believes the notion of something being biologically impossible is obsolete. Wilmut, along with colleagues at the Roslin Institute and the biotech firm PPL in Edinburgh, Scotland, in 1996 created the first mammal cloned from an adult body cell. Although there were several others (lambs that were not only cloned but genetically modified as well), Dolly became the best known. She proved that a totally differentiated adult cell contained a complete genome. Of course, it was the ideas of creating duplicates and cloning people that spawned the greatest intrigue. Surely by now, however, we all understand that even though a clone may share the donor's genetic make-up, every individual is, well, individual-the unique product of genetic, environmental and experiential inputs. Cloning is not going to be a good hedge against the things we fear most: disease and death. Nevertheless, when the topics of gene engineering, chromosome-making, stem-cell injection and genomic analysis are jumbled together, almost anything seems possible. Of course, all things are not yet possible. Even the most likely stem-cell-based regenerative medicine remains a long-range goal with many short-term research objectives still to be met. These include understanding how the cells work to generate healing from a biological perspective, and how they perform in patients. "You have to be pragmatic in your approach, as well as apply the best and most rigorous science that you can," says Clive Svendsen, director of the Cedars-Sinai Regenerative Medicine Institute in Los Angeles. "There is one group of people that says, 'We need to know everything about this before we can possibly touch a patient.' And there is another that says, 'I don't care about anything; put the cells in, because the patient is dying.' I say, let's have a rational plan backed up by statistical evidence that something has an effect; but once we get to a certain point, let's proceed with that 'something' to a clinical trial."(See more of our interview, "Just Getting On With Business.") HABITS OF LIFE: While the goal of healing degenerative disease such as diabetes, Parkinson's and ALS is a hopeful and positive good end, the means of reaching that goal remains cloudy. By distracting ourselves with dystopian scenarios (of, say, new species of humans bred and grown in bottles like a production line of colas, or genetic castes designed for the duller or more dangerous jobs of the future), we may miss the real downside of what already exists. How far do we go with pre-implantation genetic analysis? What of the fate of embryo "leftovers" from in vitro fertilization clinics? Is the intentional creation and destruction of human embryos as a source of new lineages of stem cells a good idea? But we may miss the upside as well. A new embryo-like stem cell, called an iPS cell (induced-pluripotent stem cell) can be reprogrammed from a patient's skin cell. The potential to create new cell lines useful for studying disease in human cells and not just animal models is an encouraging step. The idea is to "recapitulate" the course of disease, says Fred Gage of the Salk Institute in San Diego, with the aim of learning how the disease happened, the interplay of genes and biochemistry. True cures will be possible only if the actual workings of the diseased cells are revealed. Then it may one day be possible to access those mechanisms and retune them. While many biologists take the reductionist view of disease-looking for the chemical switches to shut down problems and restart normal function-we know this is incomplete. "I think disease is totally a matter of context," Susan Fitzpatrick, vice president of the James S. McDonnell Foundation, told Vision. Our problems may have cellular markers, but is what we see a cause or an effect? "Aspects of a particular question can be explored in models," she says, but "at some point it all has to be brought back to a cell in a tissue, in an organ, in an organism, and the interactions at every level with the various environments encountered." Clearly there are broad influences that contribute to a person's vulnerability to degenerative diseases. Because many are age-related, it would also make sense to seek out the characteristics common to healthy seniors. Dan Buettner, explorer and National Geographic writer, traveled the world to study pockets of centenarians. Collecting his findings in his book The Blue Zones, Buettner focused on lifestyle, not cells. Rather than excising broken tissue or bombarding the body with toxins to subdue wayward cells, Buettner suggests a different clinical path. "Cut out the toxic people in your life," he advises, "and spend time and effort augmenting your social circle with people who have the right values and a healthy lifestyle." (See "Live Long and Prosper.") Leon Kass, chairman of the President's Council on Bioethics from 2001 to 2005, adds that quality of life also means more than being free of disease. "It is not mere life, or even a healthy life, but rather a good and worthy life for which we must aim. And while poor health may weaken our efforts, good health alone is an insufficient condition or sign of a worthy human life." This is a challenging statement because it asks us each to consider the purpose of life itself. What is a life for? "We must strike a proper balance," Kass continues, "a balance that can only be furthered if the approach to health also concentrates on the habits of life." A TREE IS KNOWN BY ITS FRUIT: There is a feeling that new science is necessary to fix the problems created by old science. At the heart of Venter's work is a desire not simply to repair what degenerative disease does to the body but to undo the damage we have done to the world. Even civilization itself can be seen as toxic, a pox-not simply from an ecological point of view but as itself degenerative or degenerating, teetering on the edge of collapse because we have built it with technologies whose long-term consequences we really did not understand. Venter's offering of made-to-order life is meant to facilitate positive change, a seed planted for a better future. "We need new ways to alter our future, or we aren't going to have one," he says. We have created a fast-paced, impatient world with which most of us are deeply intertwined and on which all of us depend-a dependence that goes beyond the interchange of food and water. Our wired umbilicals interconnect, rooted in human systems and cultures, thirsty for pulses of electronic media that power our working and leisure lives. When we have a free moment, a weekend perhaps, we want to go-go-go some more. But there is little time to think, and even less time to consider how this hectic pace changes and affects us psychologically and physically. The point of a poem, and the enduring appreciation for the timelessness of a poet such as Frost, is that it provides something to think about, a pause worth taking. In our science- and technology-driven world, we seldom have a moment to reflect and consider that it is not the scientist but the artist who has the better grip on ambition and the drivers of human nature. Maybe we live in a comfort zone of naïve trust, unwilling to attend to the challenges brought about by our discoveries and our desires, hopeful that others might determine the boundary lines. "Biotechnology," suggests the "Beyond Therapy" report, "like any other technology, is not for anything in particular. Like any other technology, the goals it serves are supplied neither by the techniques themselves nor by the powers they make available, but by their human users. Like any other means, a given biotechnology once developed to serve one purpose is frequently available to serve multiple purposes, including some that were not imagined or even imaginable by those who brought the means into being." Yes, there are roughly zones. While our desires to investigate may be boundless, and we may feel that limits exist only to be overcome, we need to corral and temper those desires. Not all ideas will lead to where we want to go. That curiosity is the accelerator of human invention is undisputed; it makes us who we are and is at the core of all we do and have done. But an accelerator needs to be paired with a brake, a means to slow down, so we have time to judge and adjust. After all, contentment is also a healer. A wise planter does not plant with abandon, without thoughtfulness; he selects his field and the appropriate crop carefully. Pushing forward without doing so, he knows, would yield bitter fruit. DAN CLOER dan.cloer@visionjournal.org Source: www.vision.org SELECTED REFERENCES: 1 Ronald Bailey, Liberation Biology: The Scientific and Moral Case for the Biotech Revolution (2005). 2 Dan Buettner, The Blue Zones: Lessons for Living Longer From the People Who've Lived the Longest (2008). 3 Leon Kass, Toward a More Natural Science: Biology and Human Affairs (1985). 4 Bill McKibben, Enough: Staying Human in an Engineered Age (2003). 5 The President's Council on Bioethics, "Beyond Therapy: Biotechnology and the Pursuit of Happiness" (2003). 6 Ian Wilmut, Keith Campbell and Colin Tudge, The Second Creation: Dolly and the Age of Biological Control (2000).