Products of value from cells' machinery

November 04, 1991|By Michael Pollick

What's all the excitement about biotechnology? It is about being able to manipulate the cellular machinery of life to create products of value: pharmaceuticals and diagnostics.

Until the mid-1970s, this cellular machinery, which works the same way for all living things, was really a black box. It didn't lend itself to manipulation.

If you think of the human being as a computer, the extremely long molecule called DNA that is contained in every one of our cells is like the software system. It works like a hard disk on a computer, and it contains all the information that your body will ever use in its lifetime.

The DNA molecule, which is not as neat and pretty as it is typically shown in diagrams, actually consists of about 10 billion base molecules strung together.

Inside a computer, all the data and programming is written in binary language. A long combination of 0s and 1s is used to express everything, from a letter of the alphabet to a jet fighter simulator. In a similar way, the DNA string uses four instead of two signals to express information. So just four different types of base molecules (designated A, C, T and G) are used to express everything from the way an ear lobe should look to how the body should give itself immunity from a given virus.

The body uses this coded information in DNA to make RNA and then instructs the RNA to make protein.

Proteins, which are designed to accomplish specific actions, are the goods and services of this body factory. Most people have some familiarity with the idea of proteins, which are made of amino acids. When you do a blood chemistry, you're analyzing proteins. Hemoglobin is a protein whose job is to transport oxygen. Insulin is a protein whose job is to degrade sugar. Antibodies are proteins that are custom-made by the body to fight infections.

All the targets of the new-age biopharmaceutical companies are proteins. Two examples are interleukin I and interferon II. They are extremely valuable as pharmaceuticals.

But they couldn't be made until scientists understood how to go back, find the piece of DNA that contained the information to make that protein, and then take that piece of DNA, cut it out of this string of 10 billion, stick it into a circular piece of DNA, put it into a bacterial cell, and grow it.

In the mid-1970s, the technology to accomplish this was introduced. It is called recombinant DNA technology. You find the piece of DNA with the information that will make copies of the protein you want. You cut it out, and put it in a loop of DNA that goes into a harmless bacteria cell in a laboratory dish, and you grow it.

You're exploiting bacteria to manufacture a highly valuable product. You trick them into producing something that they don't really need.

To do these manipulations, you need molecular-level tools, the most important family of which are called restriction enzymes. These are enzymes that cut DNA at specific points. They have a memory that can look for the right molecular coding point at which to slice the DNA.

They only cut if they see that sequence. So once a scientist figures out where his target gene is, he looks for cut sites upstream and downstream from that sequence. And then he uses other enzymes to combine this fragment of DNA with a utility fragment of DNA in the bacteria cell.

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