507 Eugenia Avenue
Madison 5, Wis.
November 24, 1957

Dear Joes

Well, we've just gotten back! There's no point repeating that our
trip was a stimulating experience, some of it enjoyable in a simple
sense, some of it (like the Indian refugee slums in Calcutta) almost
traumatically distasteful, but pert of the world we inhabit— or that
being home has its pleasures too, though I do shudder et the pile
of work ahead for the next several months.

Your letter of November 1 graced my return. Thanke to you and Amel
for the item in the last paragraph, I hope my services will be as
worthwhile to you and the Cpppany, in the long run, as the task has
been provocative and interesting to me.

There are a number of things I want to talk to you about, and as you
will probably find it inconvenient to travel out here (though I hope you
will sanetime, so we can exchange kedachromes at 30 paces) I will try to
manage a trip to Syracuse. I have to. go to NY for a Harvey Lecture (wich
will probably be mainly en L forms etc) on December 19, and I wonder if
it would be convenient if I visited you on the 20th or 21st? If you can
say yes, I will do my best to manage it, but I better had not make a definite
commitment just yet, till I see what's awaiting me at the lab,

I'd semd you a record on this, but I have a spot of laryngitis.

MAK Which reminds me: you do have a technical librarian who ean do
literature searches etc., don't you? My expectation is based on Naomi
Cohn's description of her job before she same to Wisconsin— she has,
by the way, gone to the Roeky Mountain Rickettsia Lab of the PHS. Any
how there are a couple of items that might be worthwhile surveying in
preparation for our discussion, to wits

1. There's a fad in vogue in Australia just now for treating colds
with very large dosesof ascorbic acid. I doen't kmow if there's anything
in it, but the first time I've had an unmistakable nasal cold abert
was under the regime, is Can you find out whether they have been eny
climical triale-- there must have been with all the fuss about lemon juice
a few years ago. (I have to add that I used up the bottle en route and
haven't troubled to replace, so my present voicelessness doean8t speak
against the case.) This is probably just nonsense, but

2. While thinking (en route fren Bombay to Rome) how such a regime
could possibly work, I remembered a note by McCarty on the inactivation
of pnedmoceccal DNA by agcorbic acid--which turned out, of course, to be |
connected somehow with the oxidation of ascorbic to dehydroascorbic, and
the conconitaht release of Ho)>. Well, this would hardly account for

the effectiveness of a systemic dose, but it¢ did suggest a notion that
youb ypethical congeners in Bristol-Myers might want to explore, namely
"BRIBTOMINIS* which would be Life-Saversa in which some of the citric acid
is replaced by ascorbic. Presumably, they could at least do no harm, and
soneone with a cold or throat irritation wante something to suck on anyhow.
I do have some lingering doubts whether peroxides, being mutagenic, might
be chronically harmful, but with the ubiquity of catalase, this seems remote
~-what I'm concerned about, of course, is possible carcinogenesia; this is
farfeetched, but ought to be leeked for.

Now, McCarty (Je Exp. Med, &1:501-514) dees quote a couple of other
inactivations by ascorbic + oxygenj I have a suspicion there may be more data
particularly for bacteria, and this would be worth having looked up, or even
tried out. A point to stress is that traces of Cu catalyse the reaction I
wouldn't advocate putting in Cu, but there might be enough in your comercial
grade citric anyhow. If not, y/ Fett might do. (Don's tell this to your ad-men,
but think of its the first scienti@ic coughdrops vitamin, antibiotic and iron for
the blood too!) A girl here, Miriam Selegi, did her Ph.B, thesis, as a matter
of fact, on the Cu catalysis, and I can look this up if the project merits
any more attenthm,

What I would strese{ is that McCarty found ascorbic acid to be rather more
potent than added H40o3 at the very list, the Bristenint would furnish a slow
continuous output.

I've buried what I thought should be 'researched' in the last paragraphs: the
> marks it,

As long as we're on peroxide and local antibiosis, do you know if notatin
(glucose oxidase) would have any applicatica in a similar context? Here you'd
start out with a neutrel mint, and let gluconic acid furnish the awid taste!
Antibiosis by notatin may give sone notion of what peroxide can do.

Aside fron respiratory infection, the other selling peint for a (harmless!)
antibiotic mint would be to counteract the presumed cariogenic effect of the
suger. .

I woula ne rather distressed if (as is hardly likely) this notion is exploited
without seme scientific justification, but there is at leest some chance of it,
and it should take no great effort to getu at least an in vitro basis, either
from the literature or in your own lab. ‘

Needless to say, this diversion is not what I mainly want to discuss with yous
on the agende ought to be (#0 you can remind me)

virus end tumor chemotherapy
‘substitution chemetherapy !

two-stage & continuous fermentation technique (or, how to get rid of unwanted
trace metals, maybe)

Yours, as ever,

Joshua Lederberg