The New Biology and
Why do Giraffes Have Long Necks?
L. Stephen Coles
Now I'm not really interested in giraffes But this question of why giraffes have long necks is not simply gratuitous. It's intended as a biological metaphor for the much deeper question of how genes articulate the phenotype (or shape) of an organism. Solving this problem is equivalent in its significance to locating "The Sorcerer's Stone," as sought by ancient alchemists. [We should hasten to mention that the other classical problem of alchemy -- turning base metals into gold -- has already been solved, at least in principle, following the subsequent discovery of The Periodic Table of the Elements. The only reason why we don't exploit this knowledge as a way to make gold today, instead of continuing to dig it out of the ground the old fashioned way, is that it would cost too much. Indeed, making gold one atom at a time and using nanotechnology to assemble atoms one-at-a-time into a gold brick would cost more than it would be worth on today's open market.]
Yet the genotype/phenotype problem is the "Holy Grail" of biology and the "Big Enchilada" of medicine all rolled into one. The solution would not just be equivalent to curing age-related neurodegenerative diseases like Alzheimer's, Parkinson's, and other forms of dementia, or curing diabetes in the elderly, it would be the solution to the problem of aging itself. When you get to be over 100 years old, why do your muscles wither away while your bones slowly turn to Jell-O (geriatric muscle frailty is called sarcopenia, while bone brittleness is called osteoporosis)? Why does your skin become tissue-paper thin? Not just your outer integument but the inner linings of miles of blood and lymph vessels throughout your body. These linings also become stiff and ridged, filled with calcified plaque like water pipes in your house that have narrowed with minerals after 100 years of service. Why do you become increasingly blind and deaf and lose your sense of smell and taste? In short, why do you become the prisoner of a body whose normal function relentlessly declines? Moreover, you don't shrivel up and die when you get old because you lack the energy needed to maintain your tissues in a youthful state; old people generally get plenty of food to eat. Instead, it has to do with the DNA programs and clocks residing in your cells. This genetic program that made you you after a certain point doesn't seem to care about you anymore. There's no conspiracy within the program itself. Providing that you're not eaten by a predator or run over by a truck and you live long enough, there's no "grim-reaper" gene waiting to do you in. The embryonic program you were born with merely runs out of things to do And in the absence of new programming, your body and all its somatic tissues become subject to the slings and arrows of environmental wear and tear (entropy), just like the Egyptian pyramids that have wore down after too many centuries of wind and rain (erosion) without the benefit of the Pharaoh's Chief Architect and his coworkers being on-call for continuing maintenance. Entropy refers to the Second Law of Thermodynamics that generally prefers disorganization to complex structures (molecules to distribute themselves uniformly) or prefers shoelaces to become untied, teeth to decay, food to rot, and everything in our bodies to deteriorate when left without a program to keep things ship shape.
But the blueprints contained in The Book of Life are not simply academic information. These programs can be rewritten to new specifications; if we knew how, we could create any phenotype we desired. After all, land mammals just 45 million years ago returned to the sea and became whales, and that's a whopping big difference in phenotype, not just a longer neck. By the way, the first primates appeared on the scene between 65 and 90 million years ago, while the first humans have been around for only about 145,000 years. Not having to protect ourselves from hungry predators, so we could have the time to look at computer screens, is a very recent luxury. The proof that a relatively simple phenotype like longevity is under the control of a few hundred genes comes from fruit fly experiments whose lifespans can be experimentally doubled (compared with wild-type flies) by means of selective breeding in just 50 generations. Comparative genomics/proteomics across many mammalian species, to be accomplished in the next decade (for example, rats vs. bats, cats vs. dogs, and, of course, chimps vs. humans, which is the "Rosetta Stone" of our Book of Life) will soon reveal why giraffes have long necks -- and along the way, why our cells fail us as we age. By implication, we will learn how to reactivate our adult stem cells. The solutions to many other problems, not just scientific, that we invest in heavily today, pale by comparison. I believe that our economic investment priorities are skewed by shameless public ignorance of just how really close we are (on the order of decades). The world of post-comparative-genomics is rarely explored as a hypothesis even in our most speculative science-fiction literature or in movies derived from them, so how could we be expected to know that it's a matter of decades, not centuries? That we need to take this investigation really seriously?
If more people appreciated how close we were, the Senate might not be planning to debate the question "When does human life begin?" as they still may [Sen. Sam Brownback (R-KS) has cosponsored Bill S. 790 that seeks to ban all forms of human cloning, even therapeutic or research cloning]. According to religious fundamentalists, the politically-correct answer to this question is "Life begins at conception." This implies that scientists must not tamper with embryos without being guilty of "murdering" innocent human beings. And, of course, this in turn would criminalize experiments based on human therapeutic cloning. For most scientists, like myself, the clump of cells in a preembryo (before implantation in the womb) once outside the body need not be treated any differently than a frozen embryo would be today. It is only their potential, when re-implanted in the uterus, that matters and is deserving of our respect. What's really important is not the literal beginning of human life but the beginning of human "personhood." And a human life could not a "person" in any sense until he or she has a nervous system (post-, not pre-implantation). Even Aristotle knew this back in 330 BC, long before the issue was taken under consideration by the US Senate.
So what really should the Senate be debating on this topic, if anything? The answer ought to be how are we going to get our best and brightest minds to work on this problem in the next five-to-ten years, so we can finally break the code? What should be our National Master Plan for Research with thoughtful milestones and sufficient funding to solve this scientific/medical/social/ethical/political problem? The longer we fail to set our priorities, the more we can hear the clock ticking. The present debate is like rearranging the deck chairs on the Titanic, while the ship sinks for all of us who have the misfortune to become too old and die.
Legitimate concerns have been expressed about whether using modern technology to stop the Titanic from sinking, so to speak, may not be the equivalent of changing the very nature of the human race. But we may also think of it as taking the next well-deserved step in human evolution. And I don't mean germ-line genetic engineering that could only matter to a hypothetical cohort in a future generation of humans. I mean that this knowledge could be immediately converted into adult stem-cell therapies capable of rejuvenating those presently living, no matter how old, who were lucky enough to have made it though the knowledge "singularity" represented by such a profound understanding of computational biology that we could apply this knowledge to ourselves.
Revised September 6, 2002.