This question is probably on the mind of many people. It's important to recognize that there is an unstated assumption underlying this question. The question assumes that transgenics are inherently different in some way that might prompt us to wonder about their long-term effects. Are GM crops really different? Obviously, the answer to that depends on how one defines a difference. Almost none of our crops grown today exists as such in nature; very few even resemble the wild ancestral plants from which they were domesticated. Virtually all our crop plants have been genetically modified by a combination of human selection of desirable phenotypes from spontaneous changes and/or human-induced mutations in DNA, without a detailed understanding of the genomic or compositional changes. Changes in DNA, or genetic modifications, underlie all crop-plant improvements. The methods of modern molecular biology that are used in the laboratory to breed transgenic plants are simply new and more precise tools that allow researchers to introduce new traits into plants. There is a substantial body of evidence that shows that transgenic breeding used to develop new GM crop varieties actually causes fewer unwanted changes in the DNA, in gene expression (transcriptome), in the proteins present in the crop plant (proteome) and in the composition of the plant (metabolome).
Said another way, transgenic plants are in every measureable way more like the plants from which they were developed than are other varieties of the same crop developed via breeding methods that were considered conventional. Research shows that transgene insertion is more precise and less disruptive to the cell's genetic makeup than other methods used in the plant-breeding laboratory, such as chemical and radiation mutagenesis. A new GM variety often contains a single, well-characterized gene that has added to 30,000 or 40,000 plant genes, while traditional varieties may contain hundreds of uncharacterized mutations and/or unknown foreign genes. And the product of that gene was considered safe. The National Academy of Sciences of the United States of America and many other countries, every credible scientific society, global regulatory bodies and expert panels from around the globe that have studied the issues have all concluded that GM crops are less likely to have suffered from unintended changes in breeding that might produce undesirable effects than are crops produced by traditional methods of breeding. So, to return to the implicit assertion that GM crops are in some way different, the best science says that they are not meaningfully different from others from a hazard or risk perspective—although it can be argued they are, if anything, less likely to contain unwanted surprises. Since comparisons are made to foods that have a history of safe use, it should also be noted here that plant breeding has proven to be a very safe process over many years.
There are technical reasons why foods prepared from individual, specific varieties of crops don’t produce adverse effects over 40–50 years. Any food is a complex mixture of thousands of compounds that are safe for consumption in the amounts present in that food (and in our total diet). It's important to recognize that every chemical, including essential vitamins and other nutrients, can be toxic if we consume too much of it. Long-term toxicity from foods is seldom observed. That's because most of the food is digested, absorbed, metabolized and excreted; the unabsorbed portion passes through our bodies unchanged and is eliminated. Unlike some chemicals, food components generally don't bio-accumulate, so no adverse effects could be seen in 40–50 years.
There are a few exceptions to this rule. For example, consumption of shark or polar bear liver over a long period of time can cause hypervitaminosis D, which can be lethal. Lathyrism is a neurological disease that results from eating certain legumes, such as Lathyrus sativus (grass peas), that contain a highly toxic compound, oxalyldiaminopropionic acid (ODAP). OADP is a structural analog of glutamate, an important neural transmitter. The composition of biotech foods is carefully studied to ensure that all components are within the ranges of concentration normally observed in that food; special attention is focused on the concentration of constituents such as vitamin D or other antinutrients that could cause adverse effects if consumed in large amounts. And, since crop composition data show that GM crops are less altered in their composition than crops produced by more disruptive, black-box, conventional breeding methods, the odds of an adverse effect arising in 50 years from the consumption of a new GM variety as part of our overall diet are less than they would be from the consumption of other varieties of the same crop—but remember, crop-plant breeding has proven to be a very safe process. We are talking about food here, not toxic waste.
What does make an important difference in human health is our diet: specifically, eating a varied diet in moderation ensures optimal health. Many studies show that a diet rich in fruits and vegetables, which are high in fiber and low in fats—especially saturated fats—is likely to produce a better health outcome 40–50 years from now. So the best food advice I can offer is: is don’t worry about GM crops; focus on eating a varied, balanced diet in moderation. And while you’re at it, get plenty of rest, avoid stress and exercise regularly. You’ll feel better and live better.
The example of using lead is not a good analogy to food, firstly because it is a single compound and not a complex mixture of chemicals, like food is. Large intakes of many pure chemicals, even food ingredients like salt or baking soda, can be lethal. Secondly, it is one of many known toxic compounds that are not known to occur in food at toxic levels—largely because the food system goes to great lengths to keep lead out of food. There certainly are many compounds, like lead and mercury, that we need to avoid because they are toxic.
With regard to long-term effects on the environment, it's important to point out that mandatory, comprehensive premarket environmental safety tests are done on GM crops before they are approved. And mandatory postmarket monitoring has demonstrated to this point in time—17 years of planting GM crops—that they have on balance less environmental impact than conventional crops and improve the sustainability of agriculture in several important ways related to water, soil and reduced greenhouse gas emissions.
So far, so good, but, as your question points out, we can't know what is going to happen in 50 years. What we do know is that if we don't use GM technology, we lose some very important benefits: we will produce less yield per acre; use more chemicals, fuel and labor; lose benefits of soil conservation and improved soil organic matter; lose the benefit of water conservation and lowered contamination of water by farm chemicals; and lose the beneficial reduction in greenhouse gases. When deciding whether or not to use a new technology, one must weigh the potential risks and benefits and not ignore the damage done by present methods. There is every reason to believe that GM agriculture is more sustainable and better for the environment in many cases.