The Singularity Is Near: When Humans Transcend Biology
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—DR. ROBERT WATERSTON, INTERNATIONAL HUMAN GENOME SEQUENCING 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 massive 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.
Life’s Computer
In the very early stages of evolution information was encoded in the structure 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 with information encoded at each position by the choice of nucleotides.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.
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. The DNA strings in a single cell would measure up to six feet in length if stretched out, but an elaborate packing method coils them to fit into a cell only 1/2500 of an inch across.
Special enzymes can copy the information on each rung by splitting each base pair and assembling 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 replications.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 result 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.8 Recent 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.
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 codes 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 each called codons, with one codon for each of twenty possible amino acids, the basic building blocks of protein. A ribosome reads the codons from the mRNA and then, using tRNA, assembles a protein chain one amino acid at a time.
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 amino-acid strands as they assume 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 accumulate, disrupting cellular functions on many levels.
Under normal circumstances, 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. Accumulations of these misformed proteins aggregate into particles called protofibrils, which are thought 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 assembled 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 × 1019 (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 all 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 amino 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 all 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 an
d 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 coauthored 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, sexual 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 passive attitude 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 Association, 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 homocysteine (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 homocysteine 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 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 bypassing 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.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).
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 multipronged 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.
Biotechnology will provide the means to actually change your genes: not just designer babies will be feasible but designer baby boomers. We’ll also be able to rejuvenate all of your body’s tissues and organs by transforming your skin cells into youthful versions of every other cell type. Already, new drug development is precisely targeting key steps in the process of atherosclerosis (the cause of heart disease), cancerous tumor formation, and the metabolic processes underlying each major disease and aging process.
Can We Really Live Forever? An energetic and insightful advocate of stopping the aging process by changing the information processes underlying biology is Aubrey de Grey, a scientist in the department of genetics at Cambridge University. De Grey uses the metaphor of maintaining a house. How long does a house last? The answer obviously depends on how well you take care of it. If you do nothing, the roof will spring a leak before long, water and the elements will invade, and eventually the house will disintegrate. But if you proactively take care of the structure, repair all damage, confront all dangers, and rebuild or renovate parts from time to time using new materials and technologies, the life of the house can essentially be extended without limit.
The same holds true for our bodies and brains. The only difference is that, while we fully understand the methods underlying the maintenance of a house, we do not yet fully understand all of the biological principles of life. But with our rapidly increasing comprehension of the biochemical processes and pathways of biology, we are quickly gaining that knowledge. We are beginning to understand aging, not as a single inexorable progression but as a group of related processes. Strategies are emerging for fully reversing each of these aging progressions, using different combinations of biotechnology techniques.
De Grey describes his goal as “engineered negligible senescence”—stopping the body and brain from becoming more frail and disease-prone as it grows older.18 As he explains, “All the core knowledge needed to develop engineered negligible senescence is already in our possession—it mainly just needs to be pieced together.”19 De Grey believes we’ll demonstrate “robustly rejuvenated” mice—mice that are functionally younger than before being treated and with the life extension to prove it—within ten years, and he points out that this achievement will have a dramatic effect on public opinion. Demonstrating that we can reverse the aging process in an animal that shares 99 percent of our genes will profoundly challenge the common wisdom that aging and death are inevitable. Once robust rejuvenation is confirmed in an animal, there will be enormous competitive pressure to translate these results into human therapies, which should appear five to ten years later.
The diverse field of biotechnology is fueled by our accelerating progress in reverse engineering the information processes underlying biology and by a growing arsenal of tools that can modify these processes. For example, drug discovery was once a matter of finding substances that produced some beneficial result without exc
essive side effects. This process was similar to early humans’ tool discovery, which was limited to simply finding rocks and other natural implements that could be used for helpful purposes. Today we are learning the precise biochemical pathways that underlie both disease and aging processes and are able to design drugs to carry out precise missions at the molecular level. The scope and scale of these efforts are vast.
Another powerful approach is to start with biology’s information backbone: the genome. With recently developed gene technologies we’re on the verge of being able to control how genes express themselves. Gene expression is the process by which specific cellular components (specifically RNA and the ribosomes) produce proteins according to a specific genetic blueprint. While every human cell has the full complement of the body’s genes, a specific cell, such as a skin cell or a pancreatic islet cell, gets its characteristics from only the small fraction of genetic information relevant to that particular cell type.20 The therapeutic control of this process can take place outside the cell nucleus, so it is easier to implement than therapies that require access inside it.
Gene expression is controlled by peptides (molecules made up of sequences of up to one hundred amino acids) and short RNA strands. We are now beginning to learn how these processes work.21 Many new therapies now in development and testing are based on manipulating them either to turn off the expression of disease-causing genes or to turn on desirable genes that may otherwise not be expressed in a particular type of cell.
RNAi (RNA Interference). A powerful new tool called RNA interference (RNAi) is capable of turning off specific genes by blocking their mRNA, thus preventing them from creating proteins. Since viral diseases, cancer, and many other diseases use gene expression at some crucial point in their life cycle, this promises to be a breakthrough technology. Researchers construct short, double-stranded DNA segments that match and lock onto portions of the RNA that are transcribed from a targeted gene. With their ability to create proteins blocked, the gene is effectively silenced. In many genetic diseases only one copy of a given gene is defective. Since we get two copies of each gene, one from each parent, blocking the disease-causing gene leaves one healthy gene to make the necessary protein. If both genes are defective, RNAi could silence them both, but then a healthy gene would have to be inserted.22