|Foresight Update 38 - Table of Contents|
The Krutch Theater on the UC Berkeley campus was the location for a gathering of 150 scientists, philosophers, computer professionals, and engaging individuals. The occasion was Extro4, the Extropy Institute's conference on Biotechnology Futures: Challenges of Life Extension and Genetic Engineering. The conference was held over the weekend of August 7 & 8, 1999. A diverse array of presentations were made, which we can only touch on in this brief report.
The rate at which age-related disorders increases depends on both genetic and environmental factors. Replicative senescence the variable loss of a cell's replicative ability with each new generation has been implicated in aging and is an area of expanding study. An infinite replicative cycle is seen in tumors and some rodent cells, and a reduced cycle has been associated with uncommon aging disorders. Understanding and controlling this cycle having the ability to both encourage and prevent cell division is critical to eliminating many forms of cancer and extending lifespan.
Dr. Judith Campisi, Senior Staff Scientist of the Cell and Molecular Biology Division of Lawrence Berkeley National Laboratory, gave the event's first presentation. She spoke on her departments' efforts to unravel the cellular and molecular basis of aging, to identify and understand the elements of genetic structure that impact the human lifespan.
Dr. Campisi suggested that the limits to reproduction may have evolved as a form of cancer protection and drew our attention to three modes of senescence: DNA damage, inappropriate oncogene expression, and telomeres.
People affected by Werner Syndrome exhibit premature aging and often suffer from at least one form of cancer. Research has indicated a "Werner gene" may be responsible for controlling the number of times that human cells are able to divide before terminal differentiation. The search for this gene is converging on a family of genes that is involved with the " degrading and unwinding" of DNA and yet is usually related to DNA repair.
For those with Bloom Syndrome, the aging deficit appears more obscure and has been linked to several different chromosomes. Bloom Syndrome has been linked to telomeres. Advanced staining techniques are revealing damage and offering high correlation to expressed behaviors.
Dr. Calvin Horley, Chief Scientist of Geron Corporation, began his presentation boldly. "There is no fixed limit to longevity," he asserted. Mortality is caused by aging mechanisms, and treatment must address both the symptoms and the underlying processes. Studies of regenerative medicine may look at the mortality (using telomerase therapy), the source of cells (using stem cells), or at histocompatibility (using nuclear reprogramming methods).
On his investigation into the growth rate of hTERT clones, Dr. Horley reported that the clones appeared normal, telomere length had been preserved, and that the simple introduction of telomerase had not introduced malignancy. This continued to be the case, even when introduction occurred late in life (within 5 doublings of senescence). Therapy caused improvements in both the maintenance and the restoration of function. Additional experiments proved that stem cells implanted in mouse muscle tissue triggered differentiation and growth of identifiable structures.
Dr. Cynthia Kenyon, of the Department of Biochemistry and Biophysics at the University of California, San Francisco, spoke of her work with the inimitable Caenorhabditis elegans.
It's public, if specialized, knowledge that mutation of the daf-2 gene (which promotes growth to adulthood) doubles the lifespan of C. elegans. Extro attendees learned that Kenyon's work has been expanded to expose daf-16 as an additional regulator in aging activity. Further examination revealed a daf-2 / daf-16 interdependency.
Kenyon also spoke on a more general level, relating a link between sensory agents and longevity. Pursuing this apparent connection using germline therapy could result in complicated and flexible treatments.
Professor John Campbell (UCLA School of Medicine) discussed just such potential in his talk on the feasibility of Germline Genetic Engineering. Changes in the germline are expressed in every cell that descends from the zygote to which that mutant gamete contributed. If an adult is successfully produced, every one of its cells will contain the mutation.
Targeted Gene Substitution is currently the preferred method for modifying DNA, and requires the corrective gene be delivered to the nucleus. Foreign DNA can enter a cell directly through injection or indirectly using chemical or electrical stimulation. Early germline efforts have produced this procedure, with its distinct, implementable steps. The disadvantages include that it is costly, intrusive, and enables only a single modification at a time.
Professor Campbell and collaborator, Dr. Gregory Stock, envision a new strategy for engineering change. This proposed "double addition" method would involve adding genetic modifications to an artificial chromosome and then adding that chromosome to the egg. If successful, this technique would offer two improvements: as a system of addition using the existing genetic system, it is less intrusive; and you may introduce many changes each time.
Campbell regards the technical concerns about advancing development as nearly solved. Inheritance is divorced from the alterations, as the gene pool would be unchanged if the chromosomal changes didn't enter the sexual cycle. A "lock" may be put on expression, if the chromosome was to remain unexpressed until the introduction of another agent, say. an artificial hormone.
Many questions remain, and we must continue to guard against the inappropriate use of these emerging technologies. The appropriate expression of the appropriate genes at the appropriate moment is a lofty goal, and there is much we don't know about gene regulation.
"The selfish gene is a fiction," challenged Bear. Humans are shaped by both competition and cooperation. Our model should include both, and Bear suggests we have underappreciated the development of the "social gene". One of the implications of a competitive system is that the strong will grow and the weak will be weeded out. How to devise a means of social apoptosis that is kind to strangers?
Technology is driving this question, and cellular immortality approaches. Individual immortality may follow shortly thereafter, and we are ill-prepared to manage this transition gracefully. Bear is concerned that we will be elevating humans to this plateau with insufficient understanding of life and death.
"Stories on immortality are lacking," Vinge agreed. This lapse in enthusiasm may be reflected in the 3/10 of a year per year gain on extended lifespan calculated by the Centers for Disease Control.
"If we can get past the start-up phase, people will like it;" Vinge says, "The real risks are all the other changes." People will become more stable and happier when released from certain time pressures, but in 15 or 20 years, superhuman intelligence may exist. Can we hope to understand these intelligences when we don't understand our own, and will they help us or hinder us in our struggle to survive and flourish?
Foresight's Chris Peterson stood up with a host of others to form a panel called "Reports from the Front". Chris caused the crowd to chuckle when she contended, "Foresight Institute is both more and less radical than ExI."
Foresight is less radical from the standpoint of the technical conferences and association with the NSF and other agencies; and more radical when comparing content. The ramifications of nanotechnology development are significant and have continued to drive advances. Social acceptance of MNT memes has brought both responsibility and respectability, which may be seen in increased government funding and is evident in the leading role being assumed by the National Science Foundation.
Foresight is responding. With a major part of Foresight's original mission increased awareness of the coming development of molecular nanotechnology accomplished, the institute is turning toward policy issues and expansion of the hypertext publishing vision explored in Engines of Creation.
Panelists were united in their support of collaborative effort. Art and science are part of the same ecosystem, and perhaps the combination of their resources would lead to a brighter future.
Past attendees of Extropy Institute conferences may have met or heard Christopher Heward, a molecular endocrinologist by day who was bitten by an aging spiral some years ago. Dr. Heward spoke on treatment of the non-disease symptoms of aging as a direct way to impact long term health and survival. He returned to report that a new Phoenix-based clinic has been established to offer extensive, personalized health recommendations to prolong the individual lifespan.
Attendees also heard from Gregory Stock on the creation of a prize, similar to the Feynman Prize, for longevity milestones. (Possible candidate goals include the creation of a DNA chip to assay aging or a heterogenous mouse strain with a doubled lifespan.)
Robert Bradbury stepped forward to remind us of the need for controls when applying the principles of nanomedicine. Roy Walford discussed his investigation of the mechanisms of aging and his experiences in caloric restriction, and still there was more.
Despite the high bandwidth exchange in the lecture hall, everyone craved more, self-assembling into groups to discuss the potentials of biotechnology, genetic, intelligence, and whatever else seemed a good idea at the time. Extro conferences have become known for their interesting material and even more interesting attendees; and like Foresight Senior Associate events, these conferences have achieved some notoriety for quality parties. This community overlaps Foresight's in many ways, and we encourage you to take a look.
Jan Heward, Jose and Beatrix Salgado share a moment with Greg Stock
Max More, Tom W. Bell, and Simon Levy: founding Directors of Extropy Institute
Roy Walford, who brought us lessons from the Biosphere
A full and rapt audience in the Krutch Theater
|Foresight Update 38 - Table of Contents | Page1 | Page2 | Page3 | Page4 | Page5|
From Foresight Update 38, originally published 30 September 1999.
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