Biotechnology Explores the Human Body’s Molecular Workings
The biotechnology industry reflects the evolution of man’s understanding of what makes life--an understanding that has accelerated at such a revolutionary pace that scientists themselves are challenged to keep abreast with breakthroughs and discoveries.
Just as mathematics has advanced from counting stones to today’s supercomputers, and just as transportation has gone from the wheel to extraterrestrial flight, the treatment of illness and disease has advanced from the haphazard, folk art application of seaweed on a sore to the very manipulation of the body’s molecules.
The current age of biotechnology was trumpeted by the 1953 discovery of the configuration of the DNA molecule. Every cell--the smallest unit of life--contains the molecule, which is so small it cannot be seen in its native form even by an electron microscope. Instead, it must be cloaked in other material so it can be gleaned by an electron microscope, or bathed in a radioactive substance so that its components can be photographically deciphered, appearing as a strip of various shades of gray.
The chemical information contained in the spiral, or double-helix, DNA molecule contains each body’s unique physical signature. Sometimes referred to as the “blueprint of life,” the complex code not only establishes our physical development but how and where the body is susceptible to an illness or disease.
DNA, or deoxyribonucleic acid, is made up of four chemical bases arranged in bonded pairs, which form the rungs of the DNA’s twisting ladder. The ladder, in turn, is made up of 3 billion chemical sub-units, which collectively are known as the “human genome.” It is the sequence of those sub-units--in the form of about 100,000 genes--that constitute an individual’s genetic makeup and make him unique.
Each cell’s DNA is bundled into 23 pairs of long, thin strands called chromosomes that, if uncoiled, would stretch 8 feet. This is the starting point of the body’s cascading chemical reactions that causes us to physically function--and malfunction.
In the early 1970s, scientists began splicing genes to one another--a process called recombinant DNA, which allows the characteristics of one species to be transferred to another, and which initially raised fears that closeted scientists would create--accidentally or not--three-eyed green monsters by tinkering where they had no business.
In the late 1970s, researchers began identifying which parts of the DNA chemical palette allow the occurrence of particular diseases. So far, scientists have identified about 4,000 specific diseases that can be traced to genetic flaws, and they wonder if each of the body’s 100,000 or so genes can be the root of one disease or another.
Today, a whole new class of drugs is based on recombinant DNA, allowing physicians to inject into the body, for instance, synthetically engineered enzymes or other chemical components that the body itself can’t create.
The hope is that, through the chemical manipulation of the DNA, mutated genes--either from birth or because of disease--can essentially be replaced by healthy ones, and that most diseases can be stopped at their very root.
Joe Sorge, president of Stratagene--a company that sells biotechnology products, including DNA analysis kits--describes this front on biotechnology in computer terms:
“The body is like the hardware, and is governed by the software--the genetic code. Until 15 years ago, we didn’t understand the genetic code, so we could only treat the hardware. Now we can rewrite the software.”
Another, albeit secondary, breakthrough in molecular-level biotechnology was the discovery that pure, single-purpose antibodies--proteins that are made naturally, and in limited quantity, by the body to battle infections--could be synthesized en masse in the laboratory. These highly concentrated, disease-fighting molecules are called monoclonal antibodies. They are so small that their presence can be detected only in tests that analyze chemical reactions that occur by their presence.
Since antibodies seek out specific cells and create their own chemical reaction, one early application of monoclonal antibodies has been in diagnostic kits. Such so-called chemical dipsticks can tell you, for instance, whether you are pregnant or have strep throat, or are inflicted with a blood-borne disease or an allergy.
A more far-reaching application of monoclonal antibodies now under intense study is their use in new therapeutic medicines.
Because particular monoclonal antibodies can attach to specific, targeted cells, the vision is to partner them with drugs so that the drugs can be delivered to specific diseased sites in the body. The offensive cells can be treated without affecting benign, bystander cells.
This would play a key role, for instance, in fighting cancer. Chemotherapy destroys malignant cancer cells--but it destroys healthy, beneficial cells as well, like some huge sledgehammer. The hope is that, with the help of monoclonal antibodies serving as precision navigators, specific disease molecules can be targeted with specific drugs.
Part and parcel of this new age of biotechnology is science’s increased understanding--at the molecular and cellular level--of what causes an illness or disease, and how to either synthesize a new drug compound, or to more quickly identify an existing one, to cure it.
Historically, pharmacologists would test any number of generally understood compounds in the lab to see what effect they might have on a particular illness. The somewhat haphazard approach in developing new medicines relied to a great extent on serendipity.
Now, as medical science’s understanding of what causes us to be ill is defined at the molecular level, researchers look for the chemical compounds that they believe may be a cure without causing toxic side effects. They find these compounds either by literally shopping for them in catalogues that list already-existing molecular compounds, or they attempt to craft an entirely new one in the laboratory.
Among the major challenges is not just finding molecular flaws in the body, but identifying and isolating which step in a complex chemical reaction created the problem, and how to intervene in that process.
Critical to that is identifying which enzymes spark certain cellular reactions, and which receptor sites on cells--molecular locks and keys--can either block or trigger certain chemical responses.
Some scientists use computers that can display three-dimensional graphics to simulate the interaction of various molecules, in order to help determine whether they’ll achieve a desired chemical effect as they “fold” into each other.
Once a candidate compound is identified, it is tested on animals. If it goes well at that stage, it is then validated on humans, first to determine whether it has toxic side effects and then to determine whether it is therapeutically beneficial. Finally, it goes to the U.S. Food and Drug Administration for approval.
It can take up to 10 years--and maybe $100 million or more--for a molecular or cellular concept to be explored and the resulting drug compound to be designed and developed in the lab and tested in clinical studies, before government approval is awarded for a new medicine.
Indeed, for all of 1990, only one new biotechnology drug was approved by the FDA. But hundreds more are being studied and readied for government review, and scientists say that, in time, the approval of these new drugs may take less time than more conventionally, pharmaceutically developed drugs.
This ability to examine illnesses and diseases at the molecular level, to design specific drugs to attack molecular targets, to use monoclonal antibodies as spotters and smart bombs, and to use recombinant DNA as the basis of new medicines, are among the hallmarks of today’s biotechnology industry.
