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I am sorry I was away when your letter of January 6th arrived so 1 have been delayed in rapiying.

The information and the naterial arrived safely and I will get started as soon as possible. It will take two or three weeks before the tests currentiy in progress will be completed.

I am assuming that first priority should be given to K-302 since isélation and extraction procedures will depend on .the test., It seems likely there will be only enough material for prelininary exploration.

C-5 will be. piaced in second priority and we will, of course, explore the dosage range first. Could you send me the structural formula of this compound?

With respect to pharnacological work which should be done prior to clinical testing, it would be nice if we could always have acute toxicity in two or three speciesi a statement of the effective dose for given effects as compared with a similar material, if one exists; and a description of symptoms noticed with toxic doses, and an opinion as to the cause of death at toxic leveis (e.g., convulsions, respiratory depression, pulmonary edema, etc; something about the gross and microscopic pathology in the animals that died). If we are to do anything other than single doses, chronic toxicity would also be requlred.

The drug should-also have a general pharmacological screening. This would include effects on blood pressure; heart rate; temperature; respiratory rate, pattern and volume; central

IN AEPLYING ASDRESS THE ATI iNsTE O taL HAL ADOITION RRSANCH CENTER U.5. POULC HIALTH SERvICE HOSMTAL P. O. 80I 2000 LERINeTON, KINTUCRT

Department of HEALTH, EDUCATION, AND WELFARE • Public Health Service NATIONAL INSTITUTES OF HEALTH 14 January 1958

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nervous system effects by gross observation; and other simple measurements such as activity cages, coordination measurements, tests for analgesia, etc.

Chronic toxicity studies should include, in addition to the above, studies on blood,. bone marrow, urine, and liver function, as well as gross pathology and microscopic pathology on all organs.

As you see, most of the above is covered, partially at least, in the information you have sent me - except for the chronic work.

Could you send me information on Abood's material?

I will have to be in Washington on February 6th. If you have any time during the afternoon of February 7th I could drop by.

With kindest personal regards,

Sincerely yours,

Harri

Harris.

Hi:rn

1-1.-58

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