The Action of Acriflavine uponBodo caudatus
Authors: Robertson Muriel 
Published: June 2009

1. A study has been made of the effect of acriflavine uponBodo caudatus. The drug has the property of producing a percentage of modified Bodos without parabasal bodies but no permanently aparabasal strains have been produced.

2. A technique was devised whereby the resistance, as judged by two different types of survival experiment, could be correlated with the percentage of modified Bodos produced when the strain is put to grow in an ascending series of concentrations of acriflavine incorporated in the culture medium.

3. The peak of the count of altered Bodos in relation to the concentration in which it occurs is found to be the index of the sensitiveness of the strain at that date. The maximum reaction as gauged by the numbers of modified Bodos produced in an untreated strain of average sensitiveness is about 70 to 80 per cent., and this occurs in so low a concentration as 1/1,000,000. 1/5,000,000 gives a count below the maximum and 1/50,000,000 produces only 1 to 4 per cent. according to the sensitiveness of the strain.

4. The mass untreated strain was originally derived from a singleBodoisolated in the autumn of 1926. This strain in 1927–28 was used as the mass untreated strain in the experiments. Its resistance was found to fluctuate from below a capacity to evolve with great difficulty in 1/50,000 to a somewhat feeble development in 1/10,000 acriflavine incorporated plates. The mass untreated strain was never able to evolve in plates containing 1/5000 acriflavine at any time.

5. Strains grown from single isolations from the untreated mass culture showed different degrees of natural resistance. The most resistant clones could develop in 1/5000 acriflavine incorporated plates, but not in 1/2000. The great importance of this natural range of resistance in estimating an acquired drug fastness is emphasized. Strains which had been made resistant could be brought to live continuously in 1/1500 acriflavine incorporated plates, but no evolution was obtained in 1/1000.

6. Evidence that drug fastness inBodo caudatusis due to the interaction of selective inheritance and the actual modification of the quality of theBodoby evolution in the drug is given. The modification is not apparently a mutation, it is a heritable piling up of changes in a particular direction.

7. A high resistance once acquired is retained through prolonged cultivation upon drug-free media. A gradual loss occurs, partly by a dilution through multiplication of the character impressed and partly by the survival of variants of less resistance to acriflavine, but of perfect viability in other circumstances and the competition of these within the strain. The loss of resistance is greatly accelerated in single cell cultures (clones) isolated from the resistant strains, but up to the present no treated strain has entirely lost the effect of the original exposures to the drug. The longest time elapsing between the creating of a partially resistant strain and its test for resistance above that of the untreated culture is one year.

8. The bearing of the data obtained inBodo caudatusupon the condition found in trypanosomiasis and upon certain aspects of chemotherapy in this group is discussed.

9.Bodo caudatusbeing an organism without conjugation and therefore without bi-parental inheritance and consequently lacking the reorganising effect that such a periodic closing of the cycle produces, affords an example of a labile organism capable of being progressively altered within certain limits under the influence of the environment.