Panoply of Emerging Therapies

A broad variety of hybrid biotechnology strategies is emerging. Consider this small sample of additional research under way:

  • Chemists from the Scripps Research Institute in the United States have identified a molecule they call reversine that appears to reprogramme ageing cells to make them youthful.33 It may be an alternative to stem cell therapies to regenerate cells and tissues that need replacement.
  • Researchers have demonstrated a method of creating dried stem cells that are revived just by adding water, providing indefinite shelf life to cells that can be used to recreate tissues such as bone, blood, and organs.34
  • One of the major challenges in medicine is getting needed nutrients, supplements, and medications into the bloodstream without having to go through the gastrointestinal tract, which often interferes dramatically with a drug's effectiveness (and may also cause digestive upset). Many medications, such as insulin, human growth hormone, and therapeutic DNA, must be introduced through painful daily injections that adversely affect a patient's quality of life. Researchers at Johns Hopkins University, Maryland, have developed plastic polymer spheres that surround tiny doses of medications and can be inhaled. The polymers dissolve inside the lungs, releasing their therapeutic cargo at the correct rate. All of the materials used are already approved by the Food and Drug Administration (FDA) in the United States, so it is likely that the approval process for this application will be simplified. Ultimately, we will have the means to easily modifying genes in the (Jaaiorluibduitis clegans worm that control insulin and modifying sex hormone levels, the life span of the test animals was expanded sixfold, the equivalent of a 500-year life span for a human.32 As we gain the ability to understand and reprogramme gene expression, reprogramming the ageing process in humans will become increasingly feasible. The idea that ageing and dying are inevitable is deeply rooted, but this age-old perspective will gradually change as gene therapies are successfully demonstrated over the next two decades.

BRIDGE THREE: NANOTECHNOLOGY AND ARTIFICIAL INTELLIGENCE

As we "reverse engineer'' (understand the principles of operation behind) our biology, we will apply our technology to augment and redesign our bodies send optimal levels of all nutrients directly into the bloodstream without requiring pills or injections.

  • The human genome on a chip is now available. An integrated "gene chip" allows researchers to determine exactly which genes are expressed in a diseased organ, compared with a healthy one, which will greatly accelerate drug discovery and the prediction of drug effects.
  • We are in the early stages of creating simulated biology to be able to discover and test drugs and other therapies in silico (in chips). There are already detailed systems that can simulate organs such as the heart using cell-by-cell simulations. The Defense Advanced Research Projects Agency (DARPA) in the United States is developing a programme that will provide a virtual army of simulated test subjects to automatically test drugs, procedures, even weapons. The goal is to simulate every aspect of the human body, incorporating all genetic and proteomic (protein expression) information on a molecular level. One of DARPA's objectives is to place a digital version of each soldier's complete body on a dog tag. If that soldier needed emergency treatment, medics would access the "virtual soldier programme" on the dog tag to immediately make lifesaving decisions. Howard Asher, director of global life sciences for Sun Microsystems, states, "We believe in 10 years we can eliminate the need for all animal studies, we can eliminate phase one and phase two clinical studies, so computationally we can model a drug or therapeutic agent in the computer against the genomic data."

and brains to extend longevity radically, enhance our health, and expand our intelligence and experiences. Much of this technological development will be the result of research into nanotechnology, a term originally coined by K. Eric Drexler in the 1970s to describe the study of objects whose smallest features are less than 100 nanometres (billionths of a metre). A nanometre equals roughly the diameter of five carbon atoms.

Robert A. Freitas jr., a nanotechnology theorist, writes, "The comprehensive knowledge of human molecular structure so painstakingly acquired during the 20th and early 21st centuries will be used in the 21st century to design medically active microscopic machines. These machines, rather than being tasked primarily with voyages of pure discovery, will instead most often be sent on missions of cellular inspection, repair, and reconstruction "3:)

Freitas points out that if "the idea of placing millions of autonomous nanobots (blood cell—sized robots built molecule by molecule) inside one's body might seem odd, even alarming, the fact is that the body already teems with a vast number of mobile nanodevices." Biology itself provides the proof that nanotechnology is feasible. As Rita Colwell, director of the National Science Foundation, Virginia, has said, "Life is nanotechnology that works." Macrophages (white blood cells) and ribosomes (molecular "machines" that create amino acid strings according to information in RNA strands) are essentially nanobots designed through natural selection. As we begin to engineer our own nanobots to repair and extend biology, we won't be constrained by biology's toolbox. Biology uses a limited set of proteins for all of its creations, whereas we can create structures that are dramatically stronger, faster, and much more intricate.

One application we'll discuss further in chapter 7, on digestion, is to disconnect the sensory and pleasurable process of eating from the biological purpose of obtaining optimal nutrition. Billions of tiny nanobots in the digestive tract and bloodstream could intelligently extract the precise nutrients we require, call for needed additional nutrients and supplements through our body's personal wireless local area network (nanobots that communicate with one another), and send the rest of the food we eat on its way to elimination.

BioMEMS. If this seems particularly futuristic, keep in mind that intelligent machines are already being injected into our bloodstreams today. There are dozens of projects under way to create bloodstream-based biological micro electromechanical systems (bioMEMS) with a wide range of diagnostic and therapeutic applications.36 There are already four major conferences devoted to these projects.37 BioMEMS devices are being designed to scout out pathogens intelligently deliver medications in precise ways.

For example, nanoengineered blood-borne devices that deliver hormones such as insulin have been demonstrated in animals.3H Similar systems could precisely deliver dopamine to the brain for Parkinsons patients, provide blood-clotting factors for patients with haemophilia, and deliver cancer drugs directly to tumour sites. One new design provides up to 20 separate reservoirs that can release the different substances at programmed times and locations in the body.3^

Kensall Wise, a professor of electrical engineering at the University of Michigan in the United States, has developed a tiny neural probe that provides precise monitoring of the electrical activity of patients with neural diseases.4" Future designs are expected to deliver drugs to precise locations in the brain as well. Kazushi Ishiyama at Tohoku University in Japan has developed microma-chines that use microscopic spinning screws to deliver drugs directly into small cancerous tumours.41

A particularly innovative micromachme developed by Sandia National Labs in the U.S. has actual microteeth with a jaw that opens and closes to trap individual cells and then implant them with substances such as DNA, proteins, or drugs.42

Complex structures at the molecular level have already been constructed. In some cases, building blocks are borrowed from nature. In fact, copying or manipulating naturally occurring molecules to accomplish specific goals is a cornerstone of present-day nanotech research. DNA turns out to be a useful structural tool because the unzipped strands can be organized into structures such as cubes, octahedrons, and more complicated designs. A team at America's Cornell University used portions of a natural enzyme, ATPase, to build a nanoscale motor. Another team at the CNRS Institute in Strasbourg, France, has successfully used carbon nanotubes to deliver a peptide into the nuclei of fibroblast cells. Many approaches are being developed for micro- and nanosize machines to perform a broad variety of tasks in the body and bloodstream.

Programmable blood. One pervasive system that has already been the subject of a comprehensive conceptual redesign is our blood. In chapter 15, "The Real Cause of Heart Disease and How to Prevent It," we will discuss a series of remarkable conceptual designs by Freitas for robotic replacements of our red blood cells, white blood cells, and platelets. Detailed analyses of these designs demonstrate that these tiny robots would be hundreds or thousands of times more capable than their natural counterparts.

Nanopower. Developing power sources for these tiny devices has already received significant research attention. MEMS (micro electromechanical systems) technology is being applied to create microscopic hydrogen fuel cells to power portable electronics and, ultimately, nanobots that will be introduced into the human body. One strategy is to use the same energy sources— glucose and ATP (adenosine triphosphate)—that power our natural nanobots, such as macrophages, a type of white blood cell that is designed to destroy harmful bacteria and viruses. A Japanese research team has developed a "bio-nano" generator that creates power from glucose in the blood. Another team at the University of Texas at Austin has developed a fuel cell that uses both glucose and oxygen in human blood.43

Continual monitoring. Sensors based on silicon nanowires have shown the potential to detect disease almost instantly.44 Using any bodily fluid, such as urine, saliva, or blood, diseases including cancer can be detected at very early stages. According to the study leader, Charles M. Lieber, professor of chemistry at Harvard University, this technology will enable you to "give a drop of blood from a pinprick on your finger and, within minutes, find out whether you have a particular virus or genetic disease, or your risk for different diseases or drug interactions.1' This approach can also be used for detection of bioterrorism threats.

Within several years, we will have the means of continually monitoring the status of our bodies to fine-tune our health programmes as well as provide early warning of emergencies such as heart attacks. The authors are working on this type of system with biomedical company United Therapeutics, using miniaturized sensors, computers, and wireless communication. Researchers at Edinburgh University are developing spray-on nanocomputers for health monitoring. Their goal: a device the size of a grain of sand that combines a computer, a wireless communication system, and sensors for heat, pressure, light, magnetic fields, and electrical currents. In another development, a research team headed by Garth Ehrlich of the Allegheny Singer Research Institute in Pittsburgh is developing MEMS-based sensor robots that can be implanted inside the body to detect infection, identify the pathogen, and then dispense the appropriate antibiotic from the device's internal containers.45

One application they envision is preventing bacterial infections, a major cause of hip joint replacement failure. Ehrlich points out that today, "the only recourse for such patients is the traumatic removal of the implant, which results in additional bone loss, extensive soft tissue destruction, months of forced bed rest with intravenous antibiotics, and significant loss of quality of life due to complete loss of mobility."

Nanosurgery. Nanobots will make great surgeons. Teams of millions of nanobots will be able to restructure bones and muscles, destroy unwanted growths such as tumours on a cell-by-cell basis, and clear arteries whilst restructuring them out of healthy tissue. Nanobots would be thousands of times more precise than the sharpest surgical tools used today, would leave no scars, and could provide continual follow-up after certain surgical procedures. Nanobot surgeons could even perform surgery on structures within cells, such as repairing DNA within the nucleus.

These nanobots will require distributed intelligence. Like ants in an ant colony, their actions will need to be highly coordinated, and the entire "colony" of nanobots will need to display flexible intelligence. Distributed systems that display intelligent coordination is one of the key goals of current research in artificial intelligence—developing computers that emulate human intelligence.

One of Freitas's more advanced conceptual designs is a DNA repair robot. Billions or even trillions of such robots could go inside all of your cells and make repairs as well as improvements to the DNA in the genes. Freitas has pointed out that it may actually be more efficient to just replace all the DNA in a gene with a new corrected copy rather than attempt to make changes to individual nucleotides.

Here's an original idea: replace the genetic machinery altogether (the cell nucleus, ribosomes, and related structures) with a small computerized robot. The computer would store the genetic code, which is only about 800 megabytes of information, or about 30 megabytes using data compression. The computerized system replacing the nucleus would then perform the function of the ribosomes by directly assembling strings of amino acids according to the computerized genetic information. These computers would all be on a wireless local area network, so improvements to the genetic code could be quickly downloaded from the Internet. It would not be necessary for the computer replacing each cell nucleus to have a complete copy of the

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