dnolosed sou gill fied sma comments on the data ;;ou wwe kiM enoqh to
  aY mw YOU have probably seen ;Ind answered the points and p38tions
Thin@! we moving Father slowly with me, exospt for tha laboratmy. A8 I

to -0

I raised.

may have slready told you, I have definitely deoided to get baak into a physiology
department or one ahere I otmM feel freer to develop along general o%llular physiology.
I had a rathar nasty experience at J:'itmOn81n mainly hoeuse it ma8 so unexpeoted.
Tbs bad of the3 department and the next ranking mesber granted all my demands 8s to
salary, ran& and aorking codlitioaa but tu dean of the Xed Sohool there turned it
down with these reported words: '1 have one Jew ahmdy on my fa5Ufty'0  Apparently
the dspartmnt head .vas entirely una.vare of the existing prejudior and got quite
exalted about it and xent to the president, Fred. Under the airaumstanaes I wouldn't
aaoetpt any appointrrrtnt in the %d. Soh. tltertr,exoept the deanship. They are however
tryinq to get me an appointmnt in the paduats faoulty in some othsr sohool. There
is on6 setup under Suslrens new head of the Botany degcatmnt  I would oonsider but
I am rather peaslmistia and besides the :&ole business has left 8 grebty baa  taste
in 3gr math, hm~

liortunaaely for my morale when I got baak fran Aladlson, f mat Ilarriaon aho

fa dean of' biologiaal soienoes at Shiftago who told me that they were definitely is
intemeted in gettirnq IPB up there and that I aould expeat 8 bid when things 866th
Born there.  By tha my, did you know that they have remntlg Urey, Fermi and myer
ma =vag froa Oolumbia and they Lare now mlng after ron I-ieumann at Prinaeton 7
As you mo=, we ham au~uireI a n(RR ah8noeller (nons other then Conipton) who is expo-
tea tG matre things hum around here when and If h61 gets here.  They are talking of
oreating a biophysiczal division whioh hm the support of Steinbaoh, &%burger and

the 3am13us no8 boauare of his frienlshlp wlth Goqton ah0 trusts his jUagmnt iinplioitly.
But ail this will t8ke tkne, probably a year.

the head Of the PhySiOS depar$.mnt, fi~heeo

Ths latter 18 Q the Way the powr on

SA any 088e I am slok and tired of soientific politias aIli Sure aould like

to get to a place .where I oculd shut the doors and .aindows of ngt laboratory a&  ?orget
all about it, I a% in an unfortunate position in that I aannot aoclept a minor position
and everybody knows it.
mast also give the opp rtunlty to build a laboratory and personnel to pU8h the
problem I have been outlining in the last few y88rs. part about it is I 3an
gat all the aoney I want and  in fact heor
$ell, so muQh for that. I shall try  BY darndest to qet us together in the same lab
as soon as I @an. Too muoh damn the is being waated.

The next position 1 moept rriust not only be pernunnent but

to turn down some in the past few months,

How are thing$ rlth you P '&at ia happening to Vlaa~her*s department ?

I notiaed that he juet lost tro of his youngpr worlrera ?

Yoms,

Comments, answere, questions.

Urpr of your quest ions dealt with the peouliaritiea observed in followlxg

the E.%. during adaptation. The fell obtained in the early period in undissimilated
oells is probably due to .a very mo. small amount of a fermentable oontdminant.  That
this Hould not be observed in disairailated oelb is to be expeoted. 3uoh oells rtore
over 80 g of any oarbotqdrate presented to them 80 that very little of this sdbstanoe
whatever it is makea its apperarsmoe as C02 via the fermentative system.

with many diffiaultiea. Jrowding effeots, th@ aooumulation of inoompletely oxidized
mtabolitee, alld other facttors poorly defined influenoe the R.Q, even in 0011s :vhen
the aomplete fermentative aystem is prersent. l'hus, suspension &loh 30ntain less than
2 ng. dry weight per 00. shor little acprobio fermentation iaa far aa the R.Q. is :on-
oerned) even with gluo088, maintaining R.Q.'8 of unity for long periods of time, ahioh
after about 4 hours begins to edoeed one. A very inforaative and sicaple experiwnt to
perform in tnis oonneotion is to take the earn aulture and make up several
staspneione of different densities (ranging from about 1 mg, to 10 mga. dry weleht per
00. and masure the R,Q. while metabolizing 2? ~SUOOBB). ixhxmxsuml  These experi-nentr
emphasize the wtoessity of always using the same densitieo #hen depending on R.2.
determination8 and indeed ff feaaable mope than one density sboilld be run in an experi
mnt.  I have use the R.J. atenaively in he1 ing rne to determine when adaptation has

rates of adaptation the only safe thing to (f !P is to take hlamgles at intervals and run
ooourrdd but these were alrays aheoEred by a

anaerobio CO ourves.
are measusin&

The use of the R.Q, alone in followirtrg the oourae of the adaptation fa fraqht

nreasuranont o rud in determining

It is more laborious but you are far more mrtain of ahat you

The inveree Pasteur phenomenon you have observed is apparently not c) general

cowomitant of the slynt?~ais of addltional fermeantative enzpms. I have not Been it
ooour in my other atrain but the om whioh you are usi@$, whioh by the way is not a
o 'revlsiae but ia Saooharcmyoea oar~ebergensis. I aent you that part iaular one beoause
it oan adapt in nitrogen aad seemed nore suitable for your heat laeasurerdnt experiments.
;IJhat the explanation is I for the life of me cannot figure out. The first thing one
Nould think of is 8 oomgetition for some aomon subatrate tit the point of divergenoe
of the tao enzyrne agrrtems and shoe tke fermentative system is more effeotive in bind-
ing substrate it becorns auoae8sful.  ftut as you oan see there are several objeationa
to such an explanation. 9ne would, in the first plaoe, expeot to find the phenomenon
muo?? ,nore aideapread than it is, In the SeOOad plaae, fermentation per se give8 rise
to substrates wNoh are perfeatly utilizabie b-7 the oxidative systems and for whlah
the fermentative enzymes would not oompete. It may be that in this partioular strain
the oxidative z~Ohm-~i8m is partioularly sensitive th inaotivstion by the produots  of
fermentatlon, :J'hy not try a little alcohol for its effect on oxygen crmsmption in thls
a tr ainl

promising. Again, however I would suggest that their effects on adaptation oould be
more surely tested if the ir taken as the measure. I would include hydrolyzed
ATP, 1.8. adenylio aoid in all experinents in whicth the effeot of the former is being
tested.  In conmotion with azide, your lower aonoentrations were not employed  in our
experimnts. In the literature @,OOl I is usually the loevest tried tb mom usual
one being 0,005'M.  In oonnedtion with these experlrcsnts there is one peauliarity
whioh nrigw be worth folloalng. Aaaording to your fig, 14 the %mmc conaentratiom
of s azide oould raise the R.Q. Of what ? Certainly not the galaatose metabolizing
system.  The fermentative system for this sugar does not as yet exist  in these oells
and so a 'pasteur phenomenon' cannot be invoked. If tb6 crells you ;EU used for these
experiment8 am undissimilated then I believe I hew the explanation.  Some time ago
I tested the effeot of oyemide, azide, and dinitrophenol on the nsturt, of the dissini-
lation of the endogenous golysaooharide reaervea. I did thia beoauee I knew that the
latter two were able to prevent the deposition or synthesir of swh reserves from

Your experiments with inhibitors and subetrates are interesting and look

%maenta eto. (2)

exogenous oarbohydrate.
rromehow shunt the enlogenous resarvea into the fermentative pathzag.
have no :onvinoing proof a8 yet I believe that this 1s slmilar in nature to the onset
of the fermentation of the elldogenous ararbohydrate in injured oells. Both the azide
and  the oyanide some why interfered with the mlntenanoe of the glyoogen a6 suoh,
it bream down and the fermentable hoxosea 08n diffuare over to the fermentative enzymes
ftraanrialtrhr,  I think it would bo vorthvhile to repeat there experinants xith both
d ioaimilated azxS un3isaimilated oells with and without aUded subatrate.
oould be easily aniawerea.

I found that dinitrophenol and to some extent azide oould

Although I

The 4ueation

     The prefidinary erperimnte on the produots 08 l$olactoae nzetabobism ~hich
you report are extre.mly inportant for the pobfera ad I would suggest that you
proaooute them ivith all goasible vlgor ergealally slnoe you are in a laboratory where
that kind of analysis is already -rtrp fairly well established.

In oonneotion with sese of your speoulations;

it has alwaye seemed to me

very unlikely, and even more so now, that the @aptation involves aqr thing at the
triose &eve1 erg. pyruvate.  After all -, ainoe the aaymnetry of gim galaotose
is in the R : OH position on tha 4th clarbon, tho xiw trioses you imuld get by aplitting
~p3lWt08e would not differ from those .#hioh you mould get by splitting jlr gluoose.
It seems to ma that the problem the oell has to solve in mstabollaing galaotorse
resides in ths first two of at rnost three ategr, i.8. until gluoose-P is formed.
QeyoM that everything is the same.  In the last few month I have been able to prove
that an enzpne Similar to hexoklnaee is forme& during ths adaptation.  1. have oalled
it 'glaQtokimse' aad it phoqhorylatea mlaotose only, no Other hexose.  I erm trying
to pin down the oarbon position of the P group and it looka now like Galaotoae-1-P.
These erperlments will once and for all la;; Low the 'bioolxamioal bogs' who wistfully
and VaEWlY 100king for the aOoutnuhtiOn of 'neaesaary intermediates' as the expla-
nation of the adaptim period. I never oould, an3 still oannot, undorstaa8 the rational
behind suzh reasoning,
speoifloity ?
*&liah ordinwily handle gluoore without mudification *. It is olear that in additton
to the galaatokinaee at least one other enzyme mat be formed mioh is probably an
Isomerase of 8ape kind.  The next step is going to be 8 great deal more dlffioult.
Primarily I an not interested  in the details of the bioohemlatry of galaotose metabolism
I agree with you however in that 38 mst know them but I awe wish erome of the bio-
ahemiata would do that job for us.  I. believe that we hare more irrgortant thizgs to
worry about.

    Don't they have any faith in their 0-m comept of enz-
Do they really believe that the same enzymes ow handle galaotoee

one of the thin- that ma ze fasalnated, due minly to tb devil in

is the follow~I

ooour& a& does not ooow in tb unadaptable 3. iudwi$ii no attier how long it la
;3rocwn on galaatosle 88 the sole aouroe of aarbon. Z'JQg in the n-0 of *Yerhof* 'Ori
an3 dl the otbr p-greates does the unadapted and maaptable Oell

a& drove them frantla with this Petty Problem*

the galaatokinase only appears in ~6118 after MaFt"tion ha'

qalacltose, whioh it doe8 very nio$lg ?

I

8 leofure UP in 'hioago to F,vms' 'qOup