Friday, March 17, 2017

Section 3–3 Biology

(Nerves / Enzymes of Krebs cycle / DNA molecules)

Feynman mentions that there is an early relationship between physics and biology in which biology helped physics in the discovery of the law of conservation of energy. This section on biology is significantly much longer as compared to other sections such as chemistry and astronomy. It could be explained by Feynman’s participation in biological research during his sabbatical year (1959 – 1960) in California Institute of Technology. It is remarkable that first-year biological students of Caltech did not know who Feynman was, and ranked Feynman as “the best teaching assistant” (Mehra, 1994, p. 441) in explaining biology. In this section, the three main ideas discussed are nerves, enzymes of Krebs cycle, and DNA molecules.

1. Nerves:
“… nerves are very fine tubes with a complex wall which is very thin; through this wall, the cell pumps ions, so that there are positive ions on the outside and negative ions on the inside, like a capacitor (Feynman et al., 1963, section 3.3 Biology).”

According to Feynman, nerves are very fine tubes (like wires) with a very thin wall (or membrane); through this wall, the cell pumps ions (sodium and potassium) to and fro such that they function like a capacitor. Essentially, when the membrane or wall “discharges” in a location, a movement of ions results in a reduction of electric voltage there. Moreover, an electrical influence on the ions in a nerve affects the membrane in which it lets the ions move along the nerve. Next, it causes a wave of “penetrability” of the membrane which runs further down the nerve fiber. This wave is like a sequence of vertical dominoes: if one domino is pushed and falls, it pushes the next and eventually all others fall. Importantly, he clarifies that the dominoes need to be re-set in order to get the nerve ready for the next nerve impulse.

The potential difference between the interior and exterior of a cell changes by about 0.1 V in a nerve impulse. Physicists’ concepts of propagating electrical phenomena in nerves (or action potentials) originate from the model of Alan Hodgkin and Andrew Huxley. They were awarded Nobel Prize in Physiology or Medicine in 1963 for their research concerning the ionic mechanisms in the nerve cell membrane. They propose the change in electrical potential in nerve membranes is due to movements of sodium and potassium ions through individual proteins (or ion channels). In his Nobel Lecture, Huxley (1963) states that a small area of membrane behaves as if it obeyed Ohm’s law. He also explains that the analysis of currents through the membranes was challenging because nerve impulses only last a fraction of a millisecond and they needed to measure the changing electrical potential at different points along the nerve.

Note: Erwin Neher and Bert Sakmann were awarded Nobel Prize in Physiology or Medicine in 1991 for their research on the function of single ion channels in cells. Note that electrical measurements were difficult in membranes since the methods available for measuring electric currents in living cells have high background noise levels. It is worth mentioning that Neher and Sakmann were well trained in physics (or biophysics). Neher studied physics at the Technische Hochschule in Munich. In University of Wisconsin at Madison, he worked in a laboratory involved in low angle X-ray scattering and was conferred a degree in biophysics. On the other hand, Sakmann was trained in cellular biophysics in University College London. His only real interests in school were physics lessons and spent much of his time designing and building model motors and sailing ships as well as remote control planes.

2. Enzymes of Krebs cycle:
“… whole series of molecules which change from one to another in a sequence or cycle of rather small steps. It is called the Krebs cycle, the respiratory cycle (Feynman et al., 1963, section 3.1 Biology).”

The Krebs cycle is a respiratory cycle (or citric acid cycle) that provides the mechanism for energy production in all forms of life. In short, it involves a whole series of molecules that change from one to another in a cycle of small steps. Feynman gives an analogy for a small step of the cycle: one molecule does not just change into another because they are usually separated by an energy barrier or “hill.” To carry an object from one location to another at the same height but on the other side of a hill, it requires the need of additional energy (activation energy) to push it over the top. Alternatively, we can also imagine holding the molecules (enzymes) in our hands and creating a hole in it to let some new atoms to roll in; thus, this way of moving around the hill does not require extra energy and the reaction is still possible.

The most important feature of the Krebs cycle is the transformation from GDP to GTP (guanosine-di-phosphate to guanosine-tri-phosphate) such that energy is stored in GTP molecules. In essence, GTP (“energy currency” molecules) has more energy than GDP and if the cycle is going in one way such that it results in more molecules which have extra energy, it can drive another process which requires energy, e.g., the contraction of muscles. Interestingly, Feynman explains that an enzyme does not care in which direction the reaction (e.g., “GDP to GTP” or “GTP to GDP”) goes because if it did it would violate one of the laws of physics. It is possible that he is referring to the reversible laws of motion instead of the second law of thermodynamics that favor irreversible processes. However, in his lectures on computation, Feynman (1996) also says that “the laws of quantum physics are reversible in time… (p. 185).”

The Krebs cycle is applicable to living beings including animals and plants. Feynman mentions that there is a machinery for absorbing light and generating glucose, which is consumed in the dark to keep plants alive. During a British Broadcasting Corporation interview, Feynman (1994) elaborates that “[p]eople look at trees and they think they come out of the ground, but really trees come out of the air. The carbon dioxide in the air goes into the tree, and it changes it: it kicks out the oxygen, pushing the oxygen away from the carbon, and leaving the carbon substance with water (p. 129).” He also clarifies that sunlight is involved during the process and says that “[i]t’s sort of ‘stored sun’ that’s coming out when you burn the log (p. 130).” In other words, trees also come from the sun and provide ‘light and heat’ when placed in a fireplace.

3. DNA molecules:
“… The DNA molecule is a pair of chains, twisted upon each other. The backbone of each of these chains, which are analogous to the chains of proteins but chemically quite different, is a series of sugar and phosphate groups (Feynman et al., 1963, section 3.3 Biology).”

Feynman explains that the structure of the DNA was studied chemically to find the composition and then with x-rays to find the pattern in space. That is, physics is of great importance in biology because it has to do with experimental techniques. Historically speaking, Francis Crick, James Watson, and Maurice Wilkins were awarded Nobel Prize in Physiology or Medicine in 1962 for their research in the molecular structure of nucleic acids and its significance for information transfer in living material. Coincidentally, Crick and Wilkins also have a strong background in physics. Crick’s unfinished Ph.D. research was on measuring the viscosity of water at high temperatures and Wilkins’s Ph.D. thesis is titled, “Phosphorescence decay laws and electronic processes in solids.” More important, Wilkins was able to achieve a better resolution of x-ray diffraction patterns as compared to those available to Pauling and other researchers.

Feynman calls adenine (A), thymine (T), cytosine (C), and guanine (G), namely, A, B, C, and D instead of A, T, C, and G. In short, he explains that only certain pairs can sit opposite each other, for example, A with B and C with D. In biology, this is known as Chargaff's second parity rule that specifies DNA molecules from any cell of all organisms should have a 1:1 ratio such that the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine. Recently, Mitchell and Bridge (2006) found that this parity rule holds for all types of double-stranded DNA genomes with the exception of the organellar DNA.

Note: During his sabbatical year (1959 – 1960), Feynman made friends with Crick, Watson, and other well-known biologists. In the section, A map of the cat of his autobiography, Feynman (1997) recalls that “Watson thought the stuff I had done with phages was of some interest, so he invited me to go to Harvard. I gave a talk to the biology department about the double mutations which occurred so close together. I told them my guess was that one mutation made a change in the protein, such as changing the pH of an amino acid, while the other mutation made the opposite change on a different amino acid in the same protein, so that it partially balanced the first imitation -- not perfectly, but enough to let the phage operate again. I thought they were two changes in the same protein, which chemically compensated each other. That turned out not to be the case… (p. 75).

Questions for discussion:
1. How do the nerves function like a capacitor?
2. Is it really true that an enzyme does not care in which direction a reaction goes because if it did it would violate one of the laws of physics?
3. How did physicists help to understand the structure of DNA molecules?

Note: The diffraction pattern due to a series of points equally spaced along a helix can be approximately modeled in terms of the squares of Bessel functions (Wilkins, Stokes, & Wilson, 1953).

The moral of the lesson: the nature of life can be reduced to all things are made of atoms, and that everything that living things do can be understood in terms of the jigglings and wigglings of atoms; physicists have also helped to build the foundations of biology by using equipment such as x-ray machines.

References:
1. Feynman, R. P. (1994). No Ordinary Genius: The Illustrated Richard Feynman. New York: W. W. Norton & Company.
2. Feynman, R. P. (1996). Feynman lectures on computation. Reading, Massachusetts: Addison-Wesley.
3. Feynman, R. P. (1997). Surely, you’re Joking, Mr. Feynman. New York: Norton.
4. Feynman, R. P., Leighton, R. B., & Sands, M. (1963). The Feynman Lectures on Physics, Vol I: Mainly mechanics, radiation, and heat. Reading, MA: Addison-Wesley.
5. Huxley, A. F. (1963). Nobel lecture: The Quantitative Analysis of Excitation and Conduction in Nerve. In Lindsten J. (ed.) Nobel Lectures in Physiology or Medicine, 1963–1970. Singapore: World Scientific.
6. Mehra, J. (1994). The Beat of a Different Drum: The life and science of Richard Feynman. Oxford: Oxford University Press.
7. Mitchell, D., & Bridge, R. (2006). A test of Chargaff’s second rule. Biochemical and biophysical research communications, 340(1), 90-94.
8. Wilkins, M. H. F., Stokes, A. R., & Wilson, H. R. (1953). Molecular structure of nucleic acids: molecular structure of deoxypentose nucleic acids. Nature, 171(4356), 738-740.

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