"Folic acid" is the popular name for a vitamin of the B group, found especially in green leafs ("folia"). In living organisms, the vitamin assumes several chemical configurations, all of which are referred to as "folates." The synthetic, stable artificial derivative used medically, is called "folic acid."

In my research work as hematologist, I was interested in the study of anemia. It was a regrettable fact that in the place where I was living there were many infants suffering from severe chronic malnutrition. During the years, I joined efforts with other researchers and together we explored several clinical aspects of those unfortunate children. From the hematological point of view, I found that the production of the bone-marrow red-cell precursors was diminished and that when adequate protein was provided, there occurred a rapid proliferation of such precursors, and that Soya protein was as good as milk in this regard. I also found signs that indicated the associated lack of the vitamin Folic Acid. Using my own modification of a method based on microbial growth to quantify it, I found that--contrary to current belief--milk contains an appreciable concentration of folic acid (folate). This discovery being of great import, I set out to clarify if the folate in milk was as biologically active to children as it was to the bacteria used for the assay. I shall not dwell on the technical details of the experiment.
However, the following is pertinent to my story, which actually has a dark human side, and a bright scientific one, in which serendipity played a role.
The bright side I may summarize as follows: The two children who served as experimental subjects had to be fed milk containing variable amounts of folate. To that effect, milk had to be made devoid of the vitamin, followed by mixing it with milk whose content was determined by means of the microbial assay. Since certain type of powdered charcoal adsorbs commercial folic acid from an aqueous suspension, I asked my technician to examine if it would work also on the biological, natural folate present as a solute in milk. She found that, indeed, milk was made free of the vitamin. And here is where serendipity enters the stage! Through a misunderstanding, the technician had boiled the milk before adding the charcoal! I told her to repeat the test using non-boiled milk. "Will it make a difference," she asked. Well, it did make a difference, for there was no adsorption from fresh milk!
I realized that the natural folate was bound to a large molecule, a protein, which was too large to be adsorbable and that heat, by denaturing it, permitted the folate to be adsorbed by the charcoal! What an euphoria: to suddenly realize that you have discovered a secret of Nature, that your name will be engraved in the Annals of Science until the sun burns down! It was clear that a new, radioactive method, was going to be developed to measure folate. I had discovered how the mammary gland concentrates the tiny amount of folate present in the blood plasma, i.e., how a biological compound is concentrated in an anatomical compartment!
This finding was soon applied to the effect of measuring folate levels in blood and tissues as it is done nowadays.

The experimental subjects were two infants who had been abandoned by their impecunious mothers. These foundlings were brought to the hospital due to some disease associated with severe malnutrition. They also suffered from folate deficiency, so that we had them transferred to our research Metabolic Ward, where they were fed a well balanced diet-except that they were given a mixture of autoclaved reconstituted milk (which I had found to be almost free of folate activity in the bioassay) with non-autoclaved regular milk. By gradually increasing the proportion of the latter, whose folate content was measured, we determined the approximate daily requirement of folate-as the deficiency signs in the bone marrow (megaloblastosis) started to recede. Then came the second part of the experiment, consisting of two phases. In the first, the milk ingested was made entirely folate-free (by charcoal adsorption of autoclaved milk); it didn't take long until the hematological manifestations of folate deficiency reappeared. At this point, folic acid was given in gradually increasing doses until improvement was again observed. The amount of folic acid (pharmacological) required for improvement was found to be roughly equivalent to the amount of folate in milk previously found to be required. Thus the bacteria growth used in the folate bioassay of milk appeared to reflect the biologic activity of the vitamin in it, as compared with the commercial folic acid, which is 100% available. It is not important to understand the cursorily written details on the nature of the experiment. The point is, the work was published in a leading journal devoted to nutritional diseases-due care being taken to include a follow- up note stating that one of the infants had been adopted by one of the attending nurses, while the other returned to his mother and was provided with dietetic supplements. No long after the paper was published, the Editor of the journal referred to my collaborator and myself a letter written by one of its readers and whose contents may be summarized as follows: " I was shocked to read in your Journal a paper delving on experiments performed on human beings. Submitting children to a diet with the express intention of developing a nutritional deficiency is unethical, to say the least."

The Editor asked for our reply and solicited our permission to publish the letter and our answer to it. I sent my answer and permission, yet did not hear anymore about that complaint or any thing else on the subject.
Here is rhe body of my reply letter: "Since the experimental procedure had a logical purpose and was conducted with decorum and within the confines of the law, we must conclude that more than unethical, our work is being qualified as unethical.
We cannot fail to understand the reasons for such judgment; we can only call the attention to the fact that we did our best to avoid irreparable damage. Also, a basically good nutritional status was assured during the critical early stages of those unfortunate infants' lives, And, most important -according to the prevailing conditions- had they not been chosen by us as experimental subjects, they would not have survived in their natural environment."