The nanotechnology inside the human body: for future medical breakthroughs, think small

The first electronic computer was a massive device. The ENIAC (Electronic Numerical Integrator And Computer, 1945) measured 30 meters long, contained 17,468 vacuum tubes, and weighed 27 metric tonnes. The ENIAC’s computational power was put to practical use in a calculation that would decide the fate of the human race. During development of the hydrogen bomb, the ENIAC determined that a thermonuclear fusion device would be 1 000 times more powerful than an atomic fission bomb and also assured physicists that testing such a weapon would NOT incinerate the Earth’s entire atmosphere. Today, the processing power of the ENIAC pales in comparison to common consumer electronic devices. Because of microelectronics, you now have much more calculating power in your hand (smart phone) or on your wrist (wearable technology). Ironically, the tremendous growth during the digital/information age is a direct result of engineering on a smaller and smaller scale.

Intel Pentium P54C die shot (600 nm process, 1995). Image: Pauli Rautakorpi via Wikimedia Commons

Much of current medicine is practiced at the macroscopic organ level with doctors specializing in the heart (cardiologists), brain (neurologists), or liver (hepatologists) for example.

However, by applying the same miniaturizing technology used in microelectronics, it is only natural to assume that future medical breakthroughs will occur at the micron scale (cellular and subcellular levels) and even smaller at the nanometer scale (molecular level).

Pharmacology, nutrition, and cell energy all occur at the nanometer (1 × 10−9 meter) level. Future advances will come from understanding what goes on deep inside human cells. The first forays into medical nanotechnology have been made in targeted delivery of medications with the hope that “magic bullet” chemotherapy will eradicate tumor cells with lower systemic toxicity.

Human energy will be another application of nanotechnology. Each of one of your cells is powered by mitochondria which generate 95% of the adenosine triphosphate (ATP) energy that powers your muscles, heart, and brain. Packed inside these miniscule mitochondria (only 0.5 to 1.0 micron in length) are complex enzyme systems that can fill an entire white board when diagramed:

• The Krebs cycle: converts food and body fat into high energy chemical intermediates via a highly efficient circular enzymatic assembly line that has the same beginning and ending substrate. When oxygen is present, fuel is burned 17 times more efficiently (34 ATP) compared to anaerobic glycolysis (2 ATP). Image by Mark Hom.
• The electron transport chain: uses the high energy molecules generated by the Krebs cycle to swap electrons between membrane-imbedded enzymes as they pump protons across the mitochondrial inner membrane. This proton battery stores energy inside the mitochondrion and is more advanced, efficient, and compact than any man-made electron battery.
• ATP synthase: is the most complicated enzyme complex in biology consisting of 31 protein sub units. Driven by the mitochondrial proton battery, this spinning nanomotor churns out ATP with components analogous to an automotive engine: The protons (fuel) can only pass the mitochondrial inner membrane by entering a channel (fuel line). As protons enter this channel, they drive the base unit (turbine rotor) of ATP synthase making it rotate. This spinning can occur at very high speed (6,000 rpm), as quickly as a high-performance automotive engine. Attached to the base is an asymmetric stalk (cam shaft) which churns the head unit. The 6 proteins in the head unit deform and mechanically generate high energy ATP from lower energy ADP (adenosine diphosphate).

ATP Synthase churns out energy. Based on an illustration from the Royal Swedish Academy of Sciences (1997). Press Release: The 1997 Nobel Prize in Chemistry. Image by Mark Hom.

This conversion of food/body fat into electrical energy into proton battery power into mechanical motion is the way ATP energy is generated. Each 360 degree complete turn of the base and stalk generates three molecules of ATP. Spinning at high speed, each ATP synthase enzyme can produce tens of thousands of molecules of ATP per minute.

The logistics are staggering. There are 37.2 trillion cells in the human body and each cell contains about one billion molecules of ATP. Such is our internal energy demand for ATP. This biologic nanomotor mechanism powers athletic performance and human vitality, far more efficiently than any man-made engine.

The complexity, compactness, and efficiency of ATP synthase is a crowning achievement of evolution. The flow of energy is what defines life and the proficient use of energy is the key to survival. If we are to learn more about human health, disease prevention, the benefits of exercise, and the aging process, we must understand the nanotechnology of energy flow inside our cells.

Mitochondria are symbiotic inhabitants of our cells, related to ancient bacteria with their own distinct DNA. Mitochondria are the masters of oxygen, capable of using the reactivity of the oxygen atom to burn sugar into CO2 and water to create usable ATP energy. Chloroplasts are symbiotic inhabitants in plants, capable of converting light, water, and CO2 into sugar (stored chemical energy). Therefore the basis of life on Earth is the cycling of carbon, oxygen, and energy between intracellular symbionts.

In Star Wars Episode I: The Phantom Menace, George Lucas explained the Force as an energy-creating symbiotic lifeform, a concept borrowed from mitochondrial biology. Just as the more powerful Star Wars characters had higher midichlorian concentrations, star athletes have more mitochondrial energy from genetics and physical training. However, Lucas got one detail wrong. Mitochondria are inherited maternally, not paternally. Therefore Darth Vader’s famous line told to Luke would have to be: “No…I am your Mother!” from Star Wars Episode V: The Empire Strikes Back.

Greg LeMond had the best mitochondrial energy of his era, powering his epic Tour de France wins. After an accidental shotgun injury, LeMond suffered from lead-induced mitochondrial myopathy that forced his early retirement from racing, making him the best case study in mitochondrial energy, both the highs and lows.

Mitochondria not only power the muscles, heart, and brain, but they also generate and neutralize the free radicals that cause aging. Our book gives practical advice explaining how to maximize mitochondrial energy with intense exercise, the molecular basis of nutrition, how to avoid common metabolic toxins, and how to slow the aging process. Our book strives to examine exercise and disease prevention at a microscopic level and in the final chapter we call for more research into the biology of human energy.

There are many genetic and acquired diseases associated with mitochondrial dysfunction and understanding them will benefit all of us. For example, why is the microelectronic industry based on electron batteries when living organisms are powered by proton batteries?

How are mitochondrial enzymes so energy efficient at the nano scale? What can be done at the molecular level to improve health and extend life? Sickle cell anemia was the first molecular disease, explained by a single errant amino acid in the hemoglobin molecule. What other diseases can be reduced to the molecular nanometer level? We will only find out if we are prepared to look smaller and smaller.

Image: Sandia Labs via Flickr.