"Why her?" is the most frequent remark one hears when observing the crowd at the Louvre, as people gape at the portrait of Lisa Gherardini, wife of Francesco del Giocondo, aka Mona Lisa. Denied the cultural means of contextualising it, deprived of reference points that would make the experience more interesting, they wonder that such an incredible fuss is made over such a small painting. A simple glimpse at Mona Lisa's silhouette, or eyes, even just her hands, brings instant recognition even to those who have no taste or passion for painting.

There are works of art that speak not only to the relatively small audience for which they were originally conceived, but to worlds beyond, to future generations, to a mass society that the artist could not even suspect would ever come into being.

It is precisely because such universal appeal cannot be separated from the system which amplifies great works and gives them resonance that one should question the idea that the success of artistic works lies only or mainly within the work itself. The western origin of so many known masterpieces suggests that they need, for their global development, appropriate political, ideological and technological support.

The renown and meanings of the Mona Lisa have been the product of a long history of political and geographical accidents, fantasies conjured up, connections made, and images manufactured.There is no single explanation for the origins and development of the global craze surrounding this painting.

That the Mona Lisa ended up in Paris in the 16th century was a decisive move, but so did many other paintings. Being painted by Leonardo da Vinci mattered considerably, but Lucrezia Crivelli, Ginevra de' Benci and Cecilia Gallerani - all prettier than Lisa Gherardini (at least by present-day standards) - were also painted by him. The famous though barely perceptible smile, now almost universally regarded as Mona Lisa's most distinctive feature, was invented by the French Romantics in the 19th century and given added resonance by Walter Pater in Britain. The theft of the painting in 1911 and its subsequent recovery in 1913 gave the Mona Lisa considerable renown, but many other stolen works of art have gained only ephemeral fame. One of the decisive factors in the relatively recent transformation of the Mona Lisa into a global icon has been its deployment in advertising, and its use in merchandising as well as by contemporary artists. But we must not forget, amid all this hype, that advertisers and artists would not have used it had it not been already highly esteemed (it was regarded as a masterpiece by many of Leonardo's own contemporaries, including Raphael).

As production becomes global and local tastes and identities are subsumed in a wider culture, advertisers need instantly recognisable symbols - the more universal, the better. We may not have an agreed definition of art, but there are universally recognisable images of what art is - and the Mona Lisa is one of them. The use of art in advertising was a way of linking a unique, high- quality object to the less-than-unique commodity being promoted. In Victorian Britain, Pears, the soap and beauty products manufacturer, devised a range of publicity schemes to beat the competition. Its greatest achievement was to use Millais's Bubbles as an advertisement for soap in 1886. This painting represented a nauseatingly pretty, curly-headed child looking at the soap bubbles he had just blown. Pears made Bubbles famous and the image was turned into postcards and jigsaw puzzles.

Advertisers found contemporary art particularly suitable. Some of it appeared to be amusing and ironic, thus contributing to the entertainment value without which advertising would be a dull affair. Besides, much contemporary art has no obvious meaning, and can be used in any way one wants. From the 1960s onward, Old Masters were also deployed: Vermeer's milkmaid found herself advertising the yogurt Chambourcy; Michelangelo's David appeared wearing Levi's jeans. The hands of Michelangelo's God creating Adam can be used by anyone simply by inserting the object to be advertised at the end of God's finger.

The Mona Lisa responded to many of the parameters set by advertisers. It certainly represented high quality because it epitomised, after all, high culture. Almost anything could be read into the features of the unknown woman portrayed. In the age of democracy, this anonymity - neither Venus nor queen, nor yet a Virgin Mary - turned out to be a positive advantage. Once Duchamp and others had distorted it in various amusing ways by adding moustaches and beard, the advertisers could follow, adding a touch of modernity. Advertising, contrary to the image the industry likes to project, is not particularly innovative. Its more successful practitioners are those who are skilled at identifying, early on, what is likely to turn into a trend or a fashion. Acumen and luck, more than creativity, are what is required. When a fashion or an idea looks like it will be productive, the entire industry joins in and, when it does so, it reinforces the general trend. It is a world where, if everybody does the same thing, everybody wins. This self-validating success is revealed in the case of the Mona Lisa. Its uses in advertising were minimal before its rise to global fame. Before 1960, there are few recorded examples of advertisements using the painting: the Italian bottled water Gioconda, the Corset Mona Lisa in the United States ("100 per cent nylon horsehair"), British-made condoms sold in Spain (Gioconda Liquid Latex "guaranteed for five years"), the Italian-made robiolina cheese Gioconda, Dutch cigars.

Then this Italian woman painted by an Italian painter was sent to Washington (1963) and Tokyo (1974) to represent French culture. By then, it had become the world's best-known picture.

Since 1980, there has been, on average, one new use found for the Mona Lisa every week: air travel (to Paris), rum, oranges, wigs, blood-testing kits, air-conditioning equipment, a dental prosthesis, the Renault Twingo, the cosmetic face mask Mudd, Marriott's Renaissance hotels, computer equipment and the intrauterine device Mona Lisa-CU375. There is a Mona Lisa hotel in Florence, as well as one in Nepal. There are Mona Lisa fridge magnets, mouse mats, clocks, hashish tins and deodorant block holders. In the US, for $14 you can buy a "Mona-Dada-Lisa" mug with Duchamp's moustache and goatee - as you fill it with hot liquid, the Frenchman's sacrilegious additions disappear and you can drink with artistic integrity.

The Mona Lisa has also offered an easy option for cartoonists trying to represent celebrities as mysterious, enigmatic and seductive. The painting's renown ensures that simply substituting the features of any celebrity for those of Lisa Gherardini amuses almost all readers of the press. The result is that anyone who is anyone has been "monalised": from Jackie Onassis to Joseph Stalin to Tony Blair. The Amis de Mona Lisa, an international association of self-styled Jocondomaniacs based in France (their motto: Jocondophiles du monde, unissez-vous) has attempted to list the Mona Lisa cartoons. The data at my disposal confirm the relatively recent origins of the craze. Only between 15 and 20 caricatures and drawings were produced before the Second World War, a few more in the period 1945-65, followed by a huge proliferation in the past 30 to 40 years.

Philately has taken a keen interest. The Mona Lisa has been used on stamps by territories as diverse as Aden, Albania, Bhutan, Bulgaria, Hungary, Jordan, North Korea, Mali, Paraguay, Qatar, Togo and the Yemen Arab Republic. Neither religion nor culture in any way distinguishes these countries, nor does politics - further evidence of the universal status gained by the Mona Lisa. Thus a work of art with impeccable high-culture credentials winds up also being the most popular. Those who bewail the imminent end of culture and civilisation should take comfort here. But they have not. They declare the Mona Lisa kitsch. The cultural establishment - like all elites - is just as ambivalent about the Mona Lisa as it is about any product of high culture that acquires vast popularity. It's as if one of the defining features of high culture is that it should be beyond the masses.

Donald Sassoon's Mona Lisa: the history of the world's most famous painting is published this month by HarperCollins (£16.99)