Genetic basis of disease apparent

Conway McLean, DPM

Diseases of the species homo sapiens (aka humans) come in all shapes and sizes. Some appear to be primarily of our own making. An obvious example would be a cigarette smoker who develops lung cancer. A lifetime consuming unhealthy foods is quite likely to lead to heart disease and clogging of the arteries. Yet, regardless of how we live our lives, and the choices we make, a critical factor in the development of disease is our genetic composition, a subject we simply don’t know enough about.

With every example provided of an individual who is diagnosed with lung cancer after years of nicotine use, there will be another about someone who smoked all their lives but had no significant consequences. What is the variable? Why do some suffer from adult-onset diabetes after years of inactivity and a lousy diet, yet others develop obesity but not diabetes. Still others, do not even take on extra weight!

The variable in all of these scenarios is each person’s genes, their DNA, the unique code that makes us each an individual. It is this genetic code, this information system, built into each cell in our body, that makes us who we are. It is also a critical factor in what type of health conditions we contract. This goes a long to explaining why some will be diagnosed with lung cancer and others have no health consequences whatsoever.

But what is “the genetic code”? Very briefly, it’s a collection of proteins inside every cell, in a VERY organized manner. It is this organization which determines what proteins are produced. As some likely know, proteins “run the ship”. They are the molecular machines that drive each and every cell. DNA, a complex biologic substance, is the instruction guide for life and its many processes. DNA is like a technical manual, instructing each cell, and every organism, on how to develop and reproduce. DNA is organized into chromosomes, each of which contains many genes. Genes are composed of DNA sequences while chromosomes are entire DNA strands packed tightly together. This arrangement makes it easier for the strand to fit into a cell.

The makeup of our genetic code clearly has a profound effect on each individual’s health. Every disease can be classified in how our genes impact the development of the condition. Some diseases are caused by alterations in a single gene, and they occur in families according to the traditional principles of inheritance.

Some diseases are classified as chromosomal, meaning they are caused by alterations in certain chromosomes. Some chromosomes may be missing, or extra chromosome copies may be present. Alternatively, certain portions of chromosomes may be deleted or duplicated. The typical and by far the most common example would be Down’s Syndrome.

The vast majority of human diseases are considered multifactorial. These are responsible for most of the chronic diseases of lifestyle that have placed such a burden on our health care system. Some examples include cardiovascular disease, cancer, and diabetes. Also classified in this category are many birth defects and psychiatric disorders. These diseases are caused by variation in many genes, and often are influenced by environment. These afflictions present the biggest challenge to geneticists. Trying to identify the genes that contribute to this expansive list of diseases has proven extremely difficult. A challenging but important goal has been to find an association between a given disease and the genetic variations leading to it.

Scientists hope to become better equipped to affect the genetic component of these disparate group of diseases. The tool being used is genetic engineering, which is the direct manipulation of an organism’s genes. This is achieved through the use of biotechnology, technologies used to change the genetic makeup of cells. They include the transfer of genes within, and across, species to produce improved or novel organisms. New DNA is obtained by either isolating and copying the genetic material of interest using recombinant DNA methods or by artificially synthesizing the DNA.

These technologies could potentially fix severe genetic disorders in humans by replacing the defective gene with a functioning one. It is an important tool in research that allows the function of specific genes to be studied. Drugs, vaccines and other products have been harvested from organisms engineered to produce them. Crops have been developed that aid food security by increasing yield, nutritional value and tolerance to environmental stresses.

The production of foods created through genetic modification is certainly a hot-button topic. These foods, referred to as GMO foods (genetically modified organisms), are defined as a living thing, be it plants, animals or microorganisms, in which the genetic material, its actual DNA, has been altered in a way that does not occur naturally by mating or by natural recombination. There must be some perceived advantage to the producer or the consumer of these foods. Most commonly, these manipulations are intended to protect crops. This may be to make crops more to resistant to plant diseases, especially those caused by insects or viruses.

The US has taken an industry-friendly position when it comes to biotechnologies and genetic manipulation. Genetic engineering is seen by some as a logical continuation of selective breeding, a long-standing practice that humans have been carrying out for years. Europe, in contrast, has instituted a more cautious approach. Many experts have concerns about these foods. A number of scientific, consumer, and environmental groups say the risks have not yet been adequately identified.

What will be the effects of genetically modified crops on health and the environment? How should such foods be labeled? What should be the role of government regulators? And more questions: is there objectivity in the research? What will be the consequence of mixing genetically modified and non-genetically modified products into the food supply?

These are serious concerns and we have few answers. What will be the effects on our biosphere and all the living organisms that compose this small globe upon which we reside. How will these creatures with altered genetic composition interact. Can we know the influence these animals will have on the environment and the organic life on the planet? We don’t know the effect on pesticide resistance, or the impact of such crops for farmers. Studies must continue on the safety of these foods. We can hope their use is cautiously introduced into the world.

In years past, the main limits to genetic engineering were technical. But we are only beginning to determine what it is possible to do. Whether we approve or not, these techniques will apparently remain in use. The long term consequences remain unknown. Do we have a moral obligation to create and use genetic engineering if it helps us to create new human medicines and feed the hungry? With global population rising exponentially, these efforts may provide the dramatic steps allowing us to feed this burgeoning mass of humanity.

Editor’s note: Dr. Conway McLean is a physician practicing foot and ankle medicine in the Upper Peninsula, with a move of his Marquette office to the downtown area. McLean has lectured internationally on wound care and surgery, being double board certified in surgery, and also in wound care. He has a sub-specialty in foot-ankle orthotics. Dr. McLean welcomes questions or comments atdrcmclean@outlook.com.