How It Was Demonstrated that Transport of Oxygen Still Requires Myoglobin

V. P. Skulachev

Department of Bioenergetics, Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-0338; E-mail: skulach@head.genebee.msu.su

---

We have already discussed [1, 2] the paradoxical observation by Garry et al. [3] that myoglobin gene knockout mice did not differ from control animals by parameters related to oxygen transport in tissues. Based on that observation, these authors questioned the generally accepted notion on the role of myoglobin in oxygen transport. One of our comments [2] presented an alternative interpretation of that data: knockout mice were suggested to mobilize some reserved mechanisms of oxygen transport. The paper by Gödecke et al. [4] appearing in the August issue of Proc. Natl. Acad. Sci. USA (1999) provided experimental evidence for this possibility. Gödecke et al. demonstrated that these mutant mice were characterized by relatively small but statistically significant changes in parameters improving oxygen delivery. Coronary flow, coronary reserve, and capillary density were increased in the mutant mice by 33, 23, and 33%, respectively, compared with control. Apparently, Garry and co-authors missed the relatively small changes in these and other relevant parameters that, however, could maintain normal functioning of the organism deficient by myoglobin as suggested by Gödecke et al. [4].

This story can serve as a good illustration for one circumstance which is well known by biologists but is often ignored by researchers who come to biology from other sciences: the amplitude of physiological responses can be relatively small, and very often our methods cannot detect them. In this connection, it is relevant to remember the wonderful epigraph used by Ephraim Racker for one of the chapters of his book Bioenergetic Mechanisms. Racker cites T. H. Huxley: “Tragedy of science: one infamous tiny fact kills an excellent hypothesis”, and then adds: “Let us, however, accept these infamous tiny facts themselves: they may represent indirect data and sometimes even artifacts. Before a verdict on the murder, we must be sure that there is a corpse. A good hypothesis costs a few infamous tiny facts and several hundreds of negative experiments” [5].

REFERENCES

1.Vinogradov, A. D. (1999) Biochemistry (Moscow), 64, 592-593.
2.Skulachev, V. P. (1999) Biochemistry (Moscow), 64, 594.
3.Garry, D. J., Ordway, G. A., Lorenz, J. N., Radford, N. B., Chin, E. R., Grange, R. W., Bassel-Duby, R., and Williams, R. S. (1998) Nature (London), 395, 905-908.
4.Gödecke, A., Flögel, U., Zanger, K., Ding, Z., Hirchenhain, J., Decking, U. K. M., and Schrader, J. (1999) Proc. Natl. Acad. Sci. USA, 96, 10495-10500.
5.Racker, E. (1967) Bioenergetic Mechanisms [Russian translation], Mir, Moscow, p. 32.

---