The price difference comes from a bunch of factors, mostly the procedures used to produce the stuff and the nature of the stuff itself.

Penicillin is produced naturally as a metabolic byproduct by penicillium molds, which can be grown easily in gi-normous vats on cheap culture medium. The medium has been specially developed to support the greatest possible fungal growth and has the right nutrients etc. along with carefully controlled environmental conditions so that the mold will produce lots of penicillin. This is mostly a computer-run, automated process. The molds producing the most penicillin weren't genetically engineered, just isolated by repeated selection of naturally occurring strains (the ancestor of which was found on a moldy cantaloupe).

The complete drug is released into the medium so it is easy to get at, and the molecule is fairly stable so it can be extracted, crystallized, stored for a long time, and other fun stuff.

Producing insulin, however, is a complicated bitch of a process which makes me thank God I'm not a diabetic, although it's a lot better process than extracting the insulin itself from cow pancreases, the pre-genetic engineering way of doing things.

It is made by cloning insulin genes into bacteria, basically forcing bacteria to uptake a mammalian insulin gene, produce the insulin, and recover it. First the insulin producing gene has to be located in human DNA (used to be cow, but now I think it's human), the gene cut out of the other DNA, copied, and delivered to bacteria by one of several vectors.

Then some bacteria are better at others than taking in foreign DNA, which then has to be incorporated into their own chromosome (bacteria have one single circular chromosome, unlike the several linear chromosomes found in other cells). Then, not all genes are active in a cell so the bacteria which successfully took in the insulin gene have to be induced to produce it and excrete it into the medium. These insulin-producing mutants have to be selected, another tedious process, and cultured. These mutant strains are then maintained in culture to avoid the cloning step, but the starter cultures have to be gradually increased in size until the culture is up to production size, smaller than the penicillin cultures. The environment has to be carefully controlled.

And now the stuff produced is not the actual insulin, but a precursor that must be collected and further refined to form insulin.

Insulin is an enzyme, which is a protein, and must have a specific shape for the molecule to be biologically active. Enzymes get their shape from chemical interactions between individual atoms in the molecule, and can get thrown out of conformation (denatured and made nonfunctional) by pH changes, temperature, chemical contaminants, and stuff like that, so processing and storing it is more complicated.

Basically it's the research & development, scut work, smaller batches, and less stable end product that drives the price up.

Hope that clears things up.

Rebecca Pinkoski