Edison was by far the most successful and, probably, the last exponent of the purely empirical method of investigation. Everything he achieved was the result of persistent trials and experiments often performed at random but always attesting extraordinary vigor and resource. Starting from a few known elements, he would make their combinations and permutations, tabulate them and run through the whole list, completing test after test with incredible rapidity until he obtained a clue. His mind was dominated by one idea, to leave no stone unturned, to exhaust every possibility.

Face this world. Learn its ways, watch it, be careful of too hasty guesses at its meaning. In the end you will find clues to it all.

He who works with the door open gets all kinds of interruptions, but he also occasionally gets clues as to what the world is and what might be important.

I trust ... I have succeeded in convincing you that modern chemistry is not, as it has so long appeared, an ever-growing accumulation of isolated facts, as impossible for a single intellect to co-ordinate as for a single memory to grasp.
The intricate formulae that hang upon these walls, and the boundless variety of phenomena they illustrate, are beginning to be for us as a labyrinth once impassable, but to which we have at length discovered the clue. A sense of mastery and power succeeds in our minds to the sort of weary despair with which we at first contemplated their formidable array. For now, by the aid of a few general principles, we find ourselves able to unravel the complexities of these formulae, to marshal the compounds which they represent in orderly series; nay, even to multiply their numbers at our will, and in a great measure to forecast their nature ere we have called them into existence. It is the great movement of modern chemistry that we have thus, for an hour, seen passing before us. It is a movement as of light spreading itself over a waste of obscurity, as of law diffusing order throughout a wilderness of confusion, and there is surely in its contemplation something of the pleasure which attends the spectacle of a beautiful daybreak, something of the grandeur belonging to the conception of a world created out of chaos.

In some sense man is a microcosm of the universe: therefore what man is, is a clue to the universe. We are enfolded in the universe.

Leakey’s work on the Olduvai Canyon man has depended a great deal on the observance of a notched break in the shinbones of good-sized animals, which is assumed to have been made by striking a bone with a sharp rock before breaking it over the knee to expose the bone marrow which is edible and nourishing. When he found broken bones with the tell-tale notch, he knew that man must have been there and so began his search.

Now, it may be stretching an analogy to compare epidemics of cholera—caused by a known agent—with that epidemic of violent crime which is destroying our cities. It is unlikely that our social problems can be traced to a single, clearly defined cause in the sense that a bacterial disease is ‘caused’ by a microbe. But, I daresay, social science is about as advanced in the late twentieth century as bacteriological science was in the mid nineteenth century. Our forerunners knew something about cholera; they sensed that its spread was associated with misdirected sewage, filth, and the influx of alien poor into crowded, urban tenements. And we know something about street crime; nowhere has it been reported that a member of the New York Stock Exchange has robbed ... at the point of a gun. Indeed, I am naively confident that an enlightened social scientist of the next century will be able to point out that we had available to us at least some of the clues to the cause of urban crime.

The discovery of an interaction among the four hemes made it obvious that they must be touching, but in science what is obvious is not necessarily true. When the structure of hemoglobin was finally solved, the hemes were found to lie in isolated pockets on the surface of the subunits. Without contact between them how could one of them sense whether the others had combined with oxygen? And how could as heterogeneous a collection of chemical agents as protons, chloride ions, carbon dioxide, and diphosphoglycerate influence the oxygen equilibrium curve in a similar way? It did not seem plausible that any of them could bind directly to the hemes or that all of them could bind at any other common site, although there again it turned out we were wrong. To add to the mystery, none of these agents affected the oxygen equilibrium of myoglobin or of isolated subunits of hemoglobin. We now know that all the cooperative effects disappear if the hemoglobin molecule is merely split in half, but this vital clue was missed. Like Agatha Christie, Nature kept it to the last to make the story more exciting. There are two ways out of an impasse in science: to experiment or to think. By temperament, perhaps, I experimented, whereas Jacques Monod thought.

The history of penicillin is one of the disgraces of medical research. Fleming published his classic paper in the British Journal of Experimental Pathology for June, 1929, but it was not until 1939 that Florey followed up the clue. An antiseptic which is almost ideal, inasmuch as it has no toxic effects, was allowed to slumber for ten years. Had it not been for the exigencies of the present war it might be slumbering still.

The phosphorous smell which is developed when electricity (to speak the profane language) is passing from the points of a conductor into air, or when lightning happens to fall upon some terrestrial object, or when water is electrolysed, has been engaging my attention the last couple of years, and induced me to make many attempts at clearing up that mysterious phenomenon. Though baffled for a long time, at last, I think, I have succeeded so far as to have got the clue which will lead to the discovery of the true cause of the smell in question.
[His first reference to investigating ozone, for which he is remembered.]

There is plenty of room left for exact experiment in art, and the gate has been opened for some time. What had been accomplished in music by the end of the eighteenth century has only begun in the fine arts. Mathematics and physics have given us a clue in the form of rules to be strictly observed or departed from, as the case may be. Here salutary discipline is come to grips first of all with the function of forms, and not with form as the final result … in this way we learn how to look beyond the surface and get to the root of things.

We are stuck with technology when all we really want is just stuff that works. How do you recognize something that is still technology? A good clue is if it comes with a manual.

We knew that DNA was important. We knew it was an important molecule. And we knew that its shape was likely to be important. But we didn’t realise I think just how important it would be. Put in other words, we didn’t realise that the shape would give us a clue to the replication mechanism. And this turned out to be really an unexpected dividend from finding out what the shape was.

When Cayley had reached his most advanced generalizations he proceeded to establish them directly by some method or other, though he seldom gave the clue by which they had first been obtained: a proceeding which does not tend to make his papers easy reading. …
His literary style is direct, simple and clear. His legal training had an influence, not merely upon his mode of arrangement but also upon his expression; the result is that his papers are severe and present a curious contrast to the luxuriant enthusiasm which pervades so many of Sylvester’s papers. He used to prepare his work for publication as soon as he carried his investigations in any subject far enough for his immediate purpose. … A paper once written out was promptly sent for publication; this practice he maintained throughout life. … The consequence is that he has left few arrears of unfinished or unpublished papers; his work has been given by himself to the world.

While playing the part of the detective the investigator follows clues, but having captured his alleged fact, he turns judge and examines the case by means of logically arranged evidence. Both functions are equally essential but they are different.

Why do I call [Isaac Newton] a magician? Because he looked on the whole universe and all that is in it as a riddle, as a secret which could be read by applying pure thought to certain evidence, certain mystic clues which God had laid about the world to allow a sort of philosopher's treasure hunt.

[American] Motherhood is like being a crack tennis player or ballet dancer—it lasts just so long, then it’s over. We’ve made an abortive effort to turn women into people. We’ve sent them to school and put them in slacks. But we’ve focused on wifehood and reproductivity with no clue about what to do with mother after the children have left home. We’ve found no way of using the resources of women in the 25 years of post-menopausal zest. As a result many women seem to feel they should live on the recognition and care of society.