Part 9 (1/2)

CHAPTER FIVE.

GNR.

Three Overlapping Revolutions

There are few things of which the present generation is more justly proud than the wonderful improvements which are daily taking place in all sorts of mechanical appliances....But what would happen if technology continued to evolve so much more rapidly than the animal and vegetable kingdoms? Would it displace us in the supremacy of earth? Just as the vegetable kingdom was slowly developed from the mineral, and as in like manner the animal supervened upon the vegetable, so now in these last few ages an entirely new kingdom has sprung up, of which we as yet have only seen what will one day be considered the antediluvian prototypes of the race....We are daily giving [machines] greater power and supplying by all sorts of ingenious contrivances that self-regulating, self-acting power which will be to them what intellect has been to the human race.-SAMUEL BUTLER, 1863 (FOUR YEARS AFTER PUBLICATION OF DARWIN'S THE ORIGIN OF SPECIES THE ORIGIN OF SPECIES Who will be man's successor? To which the answer is: We are ourselves creating our own successors. Man will become to the machine what the horse and the dog are to man; the conclusion being that machines are, or are becoming, animate.-SAMUEL BUTLER, 1863 LETTER, ”DARWIN AMONG THE MACHINES”1

The first half of the twenty-first century will be characterized by three overlapping revolutions-in Genetics, Nanotechnology, and Robotics. These will usher in what I referred to earlier as Epoch Five, the beginning of the Singularity. We are in the early stages of the ”G” revolution today. By understanding the information processes underlying life, we are starting to learn to reprogram our biology to achieve the virtual elimination of disease, dramatic expansion of human potential, and radical life extension. Hans Moravec points out, however, that no matter how successfully we fine-tune our DNA-based biology, humans will remain ”second-cla.s.s robots,” meaning that biology will never be able to match what we will be able to engineer once we fully understand biology's principles of operation.2 The ”N” revolution will enable us to redesign and rebuild-molecule by molecule-our bodies and brains and the world with which we interact, going far beyond the limitations of biology. The most powerful impending revolution is ”R”: human-level robots with their intelligence derived from our own but redesigned to far exceed human capabilities. R represents the most significant transformation, because intelligence is the most powerful ”force” in the universe. Intelligence, if sufficiently advanced, is, well, smart enough to antic.i.p.ate and overcome any obstacles that stand in its path.

While each revolution will solve the problems from earlier transformations, it will also introduce new perils. G will overcome the age-old difficulties of disease and aging but establish the potential for new bioengineered viral threats. Once N is fully developed we will be able to apply it to protect ourselves from all biological hazards, but it will create the possibility of its own self-replicating dangers, which will be far more powerful than anything biological. We can protect ourselves from these hazards with fully developed R, but what will protect us from pathological intelligence that exceeds our own? I do have a strategy for dealing with these issues, which I discuss at the end of chapter 8. In this chapter, however, we will examine how the Singularity will unfold through these three overlapping revolutions: G, N, and R.

Genetics: The Intersection of Information and Biology

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.-JAMES WATSON AND FRANCIS CRICK3 After three billion years of evolution, we have before us the instruction set that carries each of us from the one-cell egg through adulthood to the grave.-DR. ROBERT WATERSON, INTERNATIONAL HUMAN GENOME SEQUENCE CONSORTIUM4

Underlying all of the wonders of life and misery of disease are information processes, essentially software programs, that are surprisingly compact. The entire human genome is a sequential binary code containing only about eight hundred million bytes of information. As I mentioned earlier, when its ma.s.sive redundancies are removed using conventional compression techniques, we are left with only thirty to one hundred million bytes, equivalent to the size of an average contemporary software program.5 This code is supported by a set of biochemical machines that translate these linear (one-dimensional) sequences of DNA ”letters” into strings of simple building blocks called amino acids, which are in turn folded into three-dimensional proteins, which make up all living creatures from bacteria to humans. (Viruses occupy a niche in between living and nonliving matter but are also composed of fragments of DNA or RNA.) This machinery is essentially a self-replicating nanoscale replicator that builds the elaborate hierarchy of structures and increasingly complex systems that a living creature comprises. This code is supported by a set of biochemical machines that translate these linear (one-dimensional) sequences of DNA ”letters” into strings of simple building blocks called amino acids, which are in turn folded into three-dimensional proteins, which make up all living creatures from bacteria to humans. (Viruses occupy a niche in between living and nonliving matter but are also composed of fragments of DNA or RNA.) This machinery is essentially a self-replicating nanoscale replicator that builds the elaborate hierarchy of structures and increasingly complex systems that a living creature comprises.

Life's Computer

In the very early stages of evolution information was encoded in the structures of increasingly complex organic molecules based on carbon. After billions of years biology evolved its own computer for storing and manipulating digital data based on the DNA molecule. The chemical structure of the DNA molecule was first described by J. D. Watson and F. H. C. Crick in 1953 as a double helix consisting of a pair of strands of polynucleotides.6 We finished transcribing the genetic code at the beginning of this century. We are now beginning to understand the detailed chemistry of the communication and control processes by which DNA commands reproduction through such other complex molecules and cellular structures as messenger RNA (mRNA), transfer RNA (tRNA), and ribosomes. We finished transcribing the genetic code at the beginning of this century. We are now beginning to understand the detailed chemistry of the communication and control processes by which DNA commands reproduction through such other complex molecules and cellular structures as messenger RNA (mRNA), transfer RNA (tRNA), and ribosomes.

At the level of information storage the mechanism is surprisingly simple. Supported by a twisting sugar-phosphate backbone, the DNA molecule contains up to several million rungs, each of which is coded with one letter drawn from a four-letter alphabet; each rung is thus coding two bits of data in a one-dimensional digital code. The alphabet consists of the four base pairs: adenine-thymine, thymine-adenine, cytosine-guanine, and guanine-cytosine.

Special enzymes can copy the information on each rung by splitting each base pair and a.s.sembling two identical DNA molecules by rematching the broken base pairs. Other enzymes actually check the validity of the copy by checking the integrity of the base-pair matching. With these copying and validation steps, this chemical data-processing system makes only about one error in ten billion base-pair combinations.7 Further redundancy and error-correction codes are built into the digital data itself, so meaningful mutations resulting from base-pair replication errors are rare. Most of the errors resulting from the one-in-ten-billion error rate will results in the equivalent of a ”parity” error, which can be detected and corrected by other levels of the system, including matching against the corresponding chromosome, which can prevent the incorrect bit from causing any significant damage. Further redundancy and error-correction codes are built into the digital data itself, so meaningful mutations resulting from base-pair replication errors are rare. Most of the errors resulting from the one-in-ten-billion error rate will results in the equivalent of a ”parity” error, which can be detected and corrected by other levels of the system, including matching against the corresponding chromosome, which can prevent the incorrect bit from causing any significant damage.8Recent research has shown that the genetic mechanism detects such errors in transcription of the male Y chromosome by matching each Y chromosome gene against a copy on the same chromosome.9 Once in a long while a transcription error will result in a beneficial change that evolution will come to favor. Once in a long while a transcription error will result in a beneficial change that evolution will come to favor.

In a process technically called translation, another series of chemicals put this elaborate digital program into action by building proteins. It is the protein chains that give each cell its structure, behavior, and intelligence. Special enzymes unwind a region of DNA for building a particular protein. A strand of mRNA is created by copying the exposed sequence of bases. The mRNA essentially has a copy of a portion of the DNA letter sequence. The mRNA travels out of the nucleus and into the cell body. The mRNA code are then read by a ribosome molecule, which represents the central molecular player in the drama of biological reproduction. One portion of the ribosome acts like a tape-recorder head, ”reading” the sequence of data encoded in the mRNA base sequence. The ”letters” (bases) are grouped into words of three letters called codons, with one codon for each of the twenty possible amino acids, the basic building blocks of protein. A ribosome reads the codons from the mRNA and then, using tRNA, a.s.sembles a protein chain one amino acid at a time.

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The notable final step in this process is the folding of the one-dimensional chain of amino acid ”beads” into a three-dimensional protein. Simulating this process has not yet been feasible because of the enormous complexity of the interacting forces from all the atoms involved. Supercomputers scheduled to come online around the time of the publication of this book (2005) are expected to have the computational capacity to simulate protein folding, as well as the interaction of one three-dimensional protein with another.

Protein folding, along with cell division, is one of nature's remarkable and intricate dances in the creation and re-creation of life. Specialized ”chaperone” molecules protect and guide the amine-acid strands as they a.s.sume their precise three-dimensional protein configurations. As many as one third of formed protein molecules are folded improperly. These disfigured proteins must immediately be destroyed or they will rapidly acc.u.mulate, disrupting cellular functions on many levels.

Under normal circ.u.mstances, as soon as a misfolded protein is formed, it is tagged by a carrier molecule, ubiquitin, and escorted to a specialized proteosome, where it is broken back down into its component amino acids for recycling into new (correctly folded) proteins. As cells age, however, they produce less of the energy needed for optimal function of this mechanism. Acc.u.mulation of these misformed proteins aggregate into particles called protofibrils, which are though to underlie disease processes leading to Alzheimer's disease and other afflictions.10 The ability to simulate the three-dimensional waltz of atomic-level interactions will greatly accelerate our knowledge of how DNA sequences control life and disease. We will then be in a position to rapidly simulate drugs that intervene in any of the steps in this process, thereby hastening drug development and the creation of highly targeted drugs that minimize unwanted side effects.

It is the job of the a.s.sembled proteins to carry out the functions of the cell, and by extension the organism. A molecule of hemoglobin, for example, which has the job of carrying oxygen from the lungs to body tissues, is created five hundred trillion times each second in the human body. With more than five hundred amino acids in each molecule of hemoglobin, that comes to 1.5 i 1019 (fifteen billion billion) ”read” operations every minute by the ribosomes just for the manufacture of hemoglobin. (fifteen billion billion) ”read” operations every minute by the ribosomes just for the manufacture of hemoglobin.

In some ways the biochemical mechanism of life is remarkably complex and intricate. In other ways it is remarkably simple. Only four base pairs provide the digital storage for all of the complexity of human life and all other life as we know it. The ribosomes build protein chains by grouping together triplets of base pairs to select sequences from only twenty amino acids. The amine acids themselves are relatively simple, consisting of a carbon atom with its four bonds linked to one hydrogen atom, one amino (-NH2) group, one carboxylic acid (-COOH) group, and one organic group that is different for each amino acid. The organic group for alanine, for example, has only four atoms (CH3-) for a total of thirteen atoms. One of the more complex amino acids, arginine (which plays a vital role in the health of the endothelial cells in our arteries) has only seventeen atoms in its organic group for a total of twenty-six atoms. These twenty simple molecular fragments are the building blocks of al life.

The protein chains then control everything else: the structure of bone cells, the ability of muscle cells to flex and act in concert with other muscle cells, all of the complex biochemical interactions that take place in the bloodstream, and, of course, the structure and functioning of the brain.11

Designer Baby Boomers

Sufficient information already exists today to slow down disease and aging processes to the point that baby boomers like myself can remain in good health until the full blossoming of the biotechnology revolution, which will itself be a bridge to the nanotechnology revolution (see Resources and Contact Information, p. 489). In Fantastic Voyage: Live Long Enough to Live Forever, which I coauth.o.r.ed with Terry Grossman, M.D., a leading longevity expert, we discuss these three bridges to radical life extension (today's knowledge, biotechnology, and nanotechnology).12 I wrote there: ”Whereas some of my contemporaries may be satisfied to embrace aging gracefully as part of the cycle of life, that is not my view. It may be 'natural,' but I don't see anything positive in losing my mental agility, sensory acuity, physical limberness, s.e.xual desire, or any other human ability. I view disease and death at any age as a calamity, as problems to be overcome.” I wrote there: ”Whereas some of my contemporaries may be satisfied to embrace aging gracefully as part of the cycle of life, that is not my view. It may be 'natural,' but I don't see anything positive in losing my mental agility, sensory acuity, physical limberness, s.e.xual desire, or any other human ability. I view disease and death at any age as a calamity, as problems to be overcome.”

Bridge one involves aggressively applying the knowledge we now possess to dramatically slow down aging and reverse the most important disease processes, such as heart disease, cancer, type 2 diabetes, and stroke. You can, in effect, reprogram your biochemistry, for we have the knowledge today, if aggressively applied, to overcome our genetic heritage in the vast majority of cases. ”It's mostly in your genes” is only true if you take the usual pa.s.sive att.i.tude toward health and aging.

My own story is instructive. More than twenty years ago I was diagnosed with type 2 diabetes. The conventional treatment made my condition worse, so I approached this health challenge from my perspective as an inventor. I immersed myself in the scientific literature and came up with a unique program that successfully reversed my diabetes. In 1993 I wrote a health book (The 10% Solution for a Healthy Life) about this experience, and I continue today to be free of any indication or complication of this disease.13 In addition, when I was twenty-two, my father died of heart disease at the age of fifty-eight, and I have inherited his genes predisposing me to this illness. Twenty years ago, despite following the public guidelines of the American Heart a.s.sociation, my cholesterol was in the high 200s (it should be well below 180), my HDL (high-density lipoprotein, the ”good” cholesterol) below 30 (it should be above 50), and my h.o.m.ocysteine (a measure of the health of a biochemical process called methylation) was an unhealthy 11 (it should be below 7.5). By following a longevity program that Grossman and I developed, my current cholesterol level is 130, my HDL is 55, my h.o.m.ocysteine is 6.2, my C-reactive protein (a measure of inflammation in the body) is a very healthy 0.01, and all of my other indexes (for heart disease, diabetes, and other conditions) are at ideal levels.14 When I was forty, my biological age was around thirty-eight. Although I am now fifty-six, a comprehensive test of my biological aging (measuring various sensory sensitivities, lung capacity, reaction times, memory, and related tests) conducted at Grossman's longevity clinic measured my biological age at forty. 15 15 Although there is not yet a consensus on how to measure biological age, my scores on these tests matched population norms for this age. So, according to this set of tests, I have not aged very much in the last sixteen years, which is confirmed by the many blood tests I take, as well as the way I feel. Although there is not yet a consensus on how to measure biological age, my scores on these tests matched population norms for this age. So, according to this set of tests, I have not aged very much in the last sixteen years, which is confirmed by the many blood tests I take, as well as the way I feel.

These results are not accidental; I have been very aggressive about reprogramming my biochemistry. I take 250 supplements (pills) a day and receive a half-dozen intravenous therapies each week (basically nutritional supplements delivered directly into my bloodstream, thereby bypa.s.sing my GI tract). As a result, the metabolic reactions in my body are completely different than they would otherwise be.16 Approaching this as an engineer, I measure dozens of levels of nutrients (such as vitamins, minerals, and fats), hormones, and metabolic by-products in my blood and other body samples (such as hair and saliva). Overall, my levels are where I want them to be, although I continually fine-tune my program based on the research that I conduct with Grossman. Approaching this as an engineer, I measure dozens of levels of nutrients (such as vitamins, minerals, and fats), hormones, and metabolic by-products in my blood and other body samples (such as hair and saliva). Overall, my levels are where I want them to be, although I continually fine-tune my program based on the research that I conduct with Grossman.17 Although my program may seem extreme, it is actually conservative-and optimal (based on my current knowledge). Grossman and I have extensively researched each of the several hundred therapies that I use for safety and efficacy. I stay away from ideas that are unproven or appear to be risky (the use of human-growth hormone, for example). Although my program may seem extreme, it is actually conservative-and optimal (based on my current knowledge). Grossman and I have extensively researched each of the several hundred therapies that I use for safety and efficacy. I stay away from ideas that are unproven or appear to be risky (the use of human-growth hormone, for example).

We consider the process of reversing and overcoming the dangerous progression of disease as a war. As in any war it is important to mobilize all the means of intelligence and weaponry that can be harnessed, throwing everything we have at the enemy. For this reason we advocate that key dangers-such as heart disease, cancer, diabetes, stroke, and aging-be attacked on multiple fronts. For example, our strategy for preventing heart disease is to adopt ten different heart-disease-prevention therapies that attack each of the known risk factors.

By adopting such multip.r.o.nged strategies for each disease process and each aging process, even baby boomers like myself can remain in good health until the full blossoming of the biotechnology revolution (which we call ”bridge two”), which is already in its early stages and will reach its peak in the second decade of this century.