ROUND TABLE DISCUSSION 763 
shown across such cells, with the level within the cells higher than on either the mucosal or serosal 
side. This situation supports the idea that cells secrete solutes from one phase to another by 
pumping the solutes into themselves more strongly from one side than from the other. 
The force of the above experiment was increased by showing point-by-point an identical 
specificity for secretion across our barrier of Ehrlich cells and for the accumulation of amino acids 
by the same cells. We know, for example, that an a-methyl group on a neutral amino acid does 
not interfere substantially either with transport into the cells, or with the development of an 
asymmetric distribution across the cells. But with the dicarboxylic amino acids, the a-methy| 
group completely prevents accumulation, and it also stops the formation of a gradient across the 
intestinal wall. 
Similarly the same aldehydes, pyridoxal, 5-deoxypyridoxal, and 4-nitrosalicylaldehyde stimu- 
late the two types of transport. The requirement of the cells for oxygen, unless glucose or fructose 
were supplied, was identical for the two processes. The temperature optima were the same; both 
required the presence of potassium ion. Every criterion that we investigated, indicated that we 
were dealing with the same phenomenon of cellular uptake in both cases, which had, however, 
been made asymmetric in the one case so that a fraction of the total concentrative activity was 
actually realized between two separate extracellular phases. 
To me this experiment has seemed rather decisive about the matter. There are, however, other 
strong lines of evidence that one solute or another in one cell or another is actually present at a 
substantially higher free concentration inside than outside. One such line of evidence arises from 
the very high levels that can sometimes be achieved inside the cells. We have heard here about 
enormous taurine gradients in marine invertebrates in which taurine may represent 3 or 4% of 
the fresh weight of the cell. What binding structure can be present at an equivalent level? Ap- 
parently the only possible candidate is the peptide bond. Almost every peptide bond would need 
to bind one taurine to account for such a degree of accumulation. If we take into account the 
other amino acids contained in such organisms we reach even less probable requirements. 
I can also cite the transport of water that has been shown to accompany the uptake of solutes. 
The swelling of the Ehrlich cell is very nearly proportional to the magnitude of the glycine gradient 
reached by these cells. The same type of phenomenon has been shown by SistTrom for lactose 
accumulation by spheroplasts of E. coli. In both cases the cells appear to respond almost linearly 
by water uptake to changes in osmotic gradients between their interiors and their environment. 
These are perhaps the strongest lines of evidence, but there are other indications of a somewhat 
more equivocal nature, having to do with the ease with which the accumulated solute may be 
obtained from the cell in the free state, or with the necessity of metabolic energy for the uptake. 
I do not mean by these comments to urge that uphill transport be taken for granted in any 
new case. Certainly we ought to be cautious about this. Nowadays transport has become a popular 
word, and quite commonly active transport is invoked in situations where no real criterion even 
for transport has been demonstrated. Uphill transport can be produced by a wide variety of cells, 
and in certain instances uphill transport seems to be established. But we certainly have greater 
cause to deplore an excessive enthusiasm for taking active transport for granted every time a solute 
is found to be accumulated by cells, than we have for excessive doubt that the phenomenon can 
occur at all. On the other hand a uniform tendency to require quotation marks around the word 
free in free cellular amino acids seems to me unnecessarily cautious. 
REINER: It seems to me that first of all we ought to have some comparative biochemistry or 
some comparative transport chemistry, because obviously different people have been working 
with different materials. Therefore, we should try to find out how many of the differences are 
due to the different organisms that have been worked on. Differences in organisms may also in 
part explain why osmotic effects as mentioned by Dr. CHRISTENSEN occur in some but not in all 
systems. 
I would also like to say something about the basic general principles, because I don’t think it 
is quite clear as to what free or bound means. The general problem is transport between two phases. 
We may at first forget about the membranes and just consider the distribution of a solute between 
two phases. This is most easily done by a diagram in which the potential energy of the solute is 
plotted against position relative to these two phases. In each phase a given solute has a certain 
energy level due to the attractions and repulsions caused by the solvent and other components of 
the solution. At the interface perhaps there is a transition which may or may not involve a hump 
of energy. 
This gets slightly more complicated if you put in a third phase, which you call a membrane. 
It is my personal prejudice that before talking about a membrane in connection with any cell, 
I would like to see a lot of evidence that there is a discrete or nearly discrete structure at the 
interface having finite thickness. But this isn’t really important, because a membrane is 
merely an extension of these notions to three phases, of which the middle one is thinner than the 
others. 
In view of all these differences of potential energy and potential barriers the problem of transport 
References p. 777 
