Rats! Another Case of Sickle Cell Anaemia

It is difficult to argue for this objectively, especially when the culture we live in is predisposed to believing evolution.¹ This predisposition prevents people from looking at the evidence from a different angle. Time and again I hear '... it has to be true', as though wishful thinking would somehow make the evidence for evolution more substantial.

I have pointed out for several years that sickle cell anaemia is not an advance in evolutionary terms. Rather it is a loss of information which is deleterious to health under normal circumstances. I have, however, been uncomfortable when discussing the example of the resistance of rats to the poison warfarin. The rat example occurs in a homework assignment in the higher biology textbook.

While teaching about mutation last year I found an explanation of the mechanism involved.² Significantly, it also turns out to be a loss of information, rather than any improvement or increase in information.

Warfarin is an anti-coagulant (stops blood clotting) drug, used both in the treatment of thrombosis in humans and as a poison for rats and mice. Obviously the amounts administered to humans are carefully controlled, whereas the aim in giving it to rats is to kill them.

Warfarin works by interfering with the normal blood-clotting mechanism. In humans this is useful because thromboses are basically blood clots, and in controlled doses warfarin can be used therapeutically. In rats, the idea is to so interfere with the normal blood clotting that the normal rapid repair of small blood vessel leakages does not occur. The rat then dies from internal bleeding.

'Superficially ... evidence of evolution'

Warfarin was first used in Britain in 1953. It was extremely effective at killing rodents, so it was used extensively. Resistance to warfarin was first noticed in Welshpool in 1959. Similar colonies of resistant rats were also found in the United States and continental Europe. Superficially, this seemed like evidence of evolution. Indeed, I once would have accepted it. Now I would want to look a little more closely at the details of the resistance.

Looking in more detail at how warfarin causes death, researchers discovered that it interferes with the metabolism of Vitamin K. Blood clotting is extremely complex, involving at least 13 factors. Four of these, however, are dependent on Vitamin K for their activation or production. Warfarin has its effect by inhibiting an enzyme involved in the metabolism of Vitamin K (Vitamin K oxide reductase).

'... not a new gene but a damaged version of an existing one'

Resistant rats were found to have a different form of this enzyme. By being structurally different it was no longer affected by warfarin. This change to the structure of the enzyme is easily attributable to mutations in the DNA code. Does this mean that a new gene has evolved? Again, closer examination is called for.

As every biology teacher tells his pupils, enzymes are highly specific. They are designed to do a specific job. On the other hand, mutations do not 'design'. Mutations are usually either harmful or at best neutral.³ Looking at the changed enzyme, it is not surprising to see that it works less well than the original. Indeed, rats which have only this enzyme are so inefficient in their metabolism of Vitamin K that they need more of it — more than 10 times the level that a normal rat requires! Should the resistant rats fail to obtain enough Vitamin K in their diet, they will die from internal bleeding (see Fig.1). What we have is not a new, useful gene, but rather a damaged version of an existing one. The spread of the damaged gene through the population is limited by its bad effects when not paired with the normal gene.

'A rat with only the resistant enzyme will die from internal bleeding ...'

How does this tie in to sickle cell anaemia? Well, in the example of warfarin resistance, the efficiency of an enzyme is sacrificed to confer resistance to warfarin. In the example of malaria, haemoglobin's efficiency at carrying oxygen is sacrificed to confer resistance to malaria. In both cases damage to an existing gene results in resistance, but at a price. A rat with only the resistant enzyme will die from internal bleeding if it cannot obtain enough Vitamin K — even if it never encounters warfarin!

Trying to explain this gaining by losing is difficult. Perhaps an analogy will help. In England, if you have a colour television set, you require a colour TV licence, which can be a bit of a problem at £80 per year. If the colour TV were to develop a fault and only give a black and white picture, then the problem of buying a colour licence would no longer apply (a cheaper black and white licence would suffice). As an analogy it helps us understand warfarin resistance and sickle cell anaemia:

• Loss of colour, giving only black and white, means a colour licence is no longer a problem.
• Loss of normal, efficient enzyme means warfarin is no longer a problem.
• Loss of normal haemoglobin means malaria is no longer a problem.

It should be pointed out that these kinds of changes which bring about selective advantage under special conditions are not advantageous outside of those conditions. In America, black Africans taken to that country 300 years ago are estimated to have had a 22 per cent frequency of the sickle cell allele.⁴ Once they were in America the selection pressure for the faulty allele (malaria) was gone. Instead, selection would have occurred for the normal and against the faulty gene. The incidence of the damaged allele among black Americans is now about 0.25 per cent.⁵

Away from the special conditions under which damaged genes are of some advantage, the selection favours the normal fully functional gene.

Another example is the grass, Agrostis tenuis, found growing on soil around a Welsh copper mine. On the contaminated soil, a mutant variety grows without competition from the normal variety. It therefore has a selective advantage by being able to colonize soil poisonous to the normal varieties. Away from the copper-contaminated soil a normal variety is more vigorous and out-competes the mutant.⁶

While this particular model of damaged genes' giving a selective advantage does not explain all resistance, it does explain some of the better-known examples. An examination of bacterial resistance to antibiotics also shows that it does not involve the generation of new information, but the modification of existing genes.⁷

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References and footnotes

1. R.J. Rushdoony, The Word of Flux (presuppositional apologetics), Thoburn Press, Fairfax (Virginia), 1975, Appendix 1—Bootstrap Reasoning.
2. L. Burnet, Exercises in Applied Genetics, Cambridge University Press, Cambridge, 1988.
3. Dawson and Goodall, Evolution Units 10 and 11, The Open University Press, Cambridge, Walton Hall, Milton Keynes, Bath, 1981, p. 19.
4. An allele is any one of two or more genes that may occur alternatively at a given site on a chromosome.
5. Charlotte J. Avers, Genetics, PWS Publishers, Boston (Massachusetts), 1984, p. 559.
6. James Torrance, Higher Grade Biology, Hoddern & Stoughton, Sevenoaks, Kent, 1993, p. 93.
7. Carl Wieland, 'Antibiotic resistance in bacteria', Creation Ex Nihilo Technical Journal, Vol.8 Part 1, 1994, pp. 5­6.