STRs
In addition to having VNTR scattered throughout the genome, our DNA also has many places where there are short sequences of repeating nonsense bases. These segments are called STRs (for short tandem repeats) and pronounced stars. Like the VNTR, these short segments of DNA can be used for identification. Typically, there might be up to a dozen or more repeats in an individual STR.
The procedure is similar to what we’ve just described for VNTR. Restriction enzymes are used to cut the DNA on both sides of the STR and a molecular tag is attached. The segments of DNA are then allowed to move through a fluid under the influence of an electric field, and shorter segments will move faster than longer ones. At a specific point downstream, a laser is used to make the molecular tag fluoresce, and the resulting light is recorded, establishing the time of arrival of each segment of DNA. As with the VNTR technique discussed above, these arrival times can be converted into a kind of bar code and used for identification. To get the kind of accuracy now attainable by the VNTR method, scientists typically use a dozen or more STRs in each run.
GENETIC ENGINEERING
If you review the mechanism by which genes are expressed in Chapter 16, you will notice that there is nothing in the entire process that depends on whether a specific gene is part of the organism’s original DNA; all that matters is the sequence of base pairs. If, for example, a gene from a different organism (or even one manufactured in the laboratory) had been inserted into a specific organism’s DNA, then the same machinery that produces proteins from ordinary genes would produce the protein coded in the new gene as well. This fact is the basis for the process of genetic engineering.
The process starts with the use of restriction enzymes to cut DNA at places where a specific sequence of base pairs occurs. The cut is made by breaking the bond between a set of base pairs (typically three pairs) so that the DNA is broken into two pieces, each with a string of unattached bases at one end. For example, if one piece has an exposed set of bases AGT, the complementary piece will have TCA. You can think of these exposed bases as a kind of Velcro patch at the end of a segment of DNA.
If we now bring up another segment of DNA that has a Velcro patch that matches the exposed bases, it will attach itself to the exposed end of the original DNA. This attachment would take place if we brought the other half of the original DNA up and reattached it, of course, but it would also happen if the segment we brought up came from an entirely different source. All that matters is that the base pairs on the new segment match the exposed bases in the original DNA.
And of course if we can do this once for one of the exposed pieces of the original DNA, we can do it twice—once at each end of the new piece of DNA we’re adding. Thus, a new stretch of DNA will have been spliced into the original DNA of the organism. As we pointed out above, once this has been done, the ordinary molecular machinery of the cell will treat the new DNA in exactly the same way as all of the rest, and the cell will start producing the protein encoded in the new gene. This is the end product of genetic engineering.
Let’s look at an example of one of the first uses of this kind of gene splicing. Diabetes is a common and serious disease, and in some cases it must be treated by the injection of insulin. Insulin is a small protein coded for in human DNA, but it is normally produced only by cells in the pancreas. It used to be that the way we got insulin for people suffering from diabetes was to go to a slaughterhouse and collect the pancreases of dead pigs. The material would be ground up, the insulin would be extracted, and after purification, it would be injected into humans. This procedure worked most of the time, but there were often problems with patients exhibiting allergic reactions to the pig insulin.
In the 1980s, a new way of producing insulin was developed. The gene for insulin from human DNA was spliced into the DNA of a bacterium, which was then allowed to grow and multiply. Each time the cell divided, the new gene was copied along with the rest of the DNA, so that eventually there were large vats of bacteria all excreting human insulin. Today, virtually all of the insulin used in the treatment of diabetes is produced by this process of genetic engineering.
Another place where genetic engineering has seen widespread use is in agriculture. Every major agricultural crop has insect pests that can damage the plants and lower the yield of a farm. Traditionally, farmers have dealt with this problem by spraying their field with insecticides, a process that is expensive and has environmental disadvantages. Genetically engineered plants provide a way around this problem.
Some natural organisms have evolved powerful insecticides and carry the code for those insecticides in their genome. These genes are the organism’s way of protecting itself from predators. If those genes are inserted into the DNA of a crop plant, then that plant will also produce the insecticide and any insect feeding on it will be killed. In such a situation, the spraying of fields with insecticides can be reduced and even in some cases eliminated.
One example of such an organism that has evolved its own insecticide is a bacterium called Bacillus thuringiensis, or Bt. The insecticide produced by Bt does not affect mammals or birds, but does a very good job of controlling insects. In the United States, most major crops—soybeans, corn, and cotton, for example—are genetically engineered by the insertion of a Bt gene (or one like it).
Attitudes toward genetically engineered foods vary around the world. When they were first introduced, there was some fear that they would trigger allergic reactions in sensitive individuals, but that does not seem to have happened. In general, European countries ban them, although genetically engineered crops for ethanol production have been introduced in some places in Europe. When these kinds of crops are introduced elsewhere, it has been found that there is often a 10 to 50 percent increase in yields, which makes them an important weapon in the battle against hunger.
Work is well along on a second generation of genetically engineered plants. Rice, for example, can be modified to include specific vitamins, and scientists are investigating the possibility of inserting genes for antibodies to endemic diseases such as cholera into common foods like bananas. This is a fast-changing field, and we can expect to hear a great deal about it in the future.
Genetic engineering may even play a role in attacking the energy problem. On one level, we can talk about genetically engineering plants to produce more ethanol for fuels. Scientists are also working on engineering bacteria to digest the cellulose in plants, as bacteria in the guts of termites do. The goal is to use crop wastes (cornstalks, for example) to produce natural gas or ethanol. This genetic technology, if successful, would add greatly to our energy supplies without using more fossil fuels or adding net carbon dioxide to the atmosphere.
CLONING
In 1997, Ian Wilmut at the Roslin Institute in Scotland stunned the world by announcing the birth of Dolly, the first cloned mammal. Countless “Hello, Dolly” headlines greeted the new development, and since that time many other kinds of animals have been cloned.
Cloning begins with a single unfertilized egg. Normally, such an egg has only half of the DNA needed to produce an adult organism. The egg’s DNA is first removed and is then replaced by DNA taken from an adult cell from another animal of the same species. At this point, the egg has a full complement of DNA.
In Chapter 16 we saw that as an organism grows from a single fertilized egg, various stretches of DNA are turned off in each cell as the cell becomes specialized. Thus, the adult DNA that is inserted into the egg has many of its genes switched off. By some process that we do not understand, the egg can undo this switching process, producing DNA in which all genes are functional. Once that has happened, the normal growth process starts and the egg begins to divide. With each division, of course, the DNA is copied, so that all the cells carry the DNA of the animal whose DNA was originally inserted into the egg. The final product will be the birth of an animal whose DNA is identical to that of the donor. This animal is called a clone.
It is important to realize that while the D
NA of a clone is identical to the DNA of the donor, it does not mean that the clone is a copy of the original. Human twins, for example, have identical DNA but grow up to be different individuals. Some scientists stress this point by referring to clones as asynchronous twins—twins born at different times. The question of how much human behavior is determined by genetic factors and how much by the environment (the old nature-nurture problem in its modern form) is an important area of research. A complex interplay clearly exists between these factors, and the answer to this question is unlikely to be simple. If pressed, the authors of this book would guess that the result will turn out to be something like a fifty-fifty split.
The first commercial applications of cloning technology were in agriculture. For centuries, farmers have bred livestock to produce animals with valuable properties—fast growth in hogs, high marbling in beef, and so on. The normal process of gene exchange in reproduction doesn’t guarantee that an animal that has these properties will pass them on to his or her offspring. If a valuable animal is cloned, however, we can be sure that the genes we value will be present in the offspring. Both the U.S. Food and Drug Administration and the European Food Safety Authority have ruled that food products (like meat) from cloned animals could not be differentiated from those same products for non-cloned animals and so is safe for consumption.
At least a dozen different species of domestic animals have been cloned. Such animals are quite expensive—a cloned cow, for example, may cost tens of thousands of dollars and thus is much too valuable to be used for food. The primary use of such animals is in the breeding process itself, where they help to speed up the development of more desirable stock.
Another use of cloning, allied to genetic engineering, involves the use of farm animals to produce pharmaceuticals for human use. The basic idea here is to insert the gene for an important molecule (human growth hormone, for example) into the DNA of a sheep or cow and see if the molecule is present in the animal’s milk. If it is, then cloning the animal will produce a herd that is able to produce that molecule in abundance. This procedure, which has been nicknamed pharming, promises a way to produce drugs that for one reason or another are difficult to produce by ordinary techniques.
STEM CELLS
As a human being develops from a single fertilized egg, an interesting process occurs in the cells’ DNA. As the cells divide, they begin to differentiate, so that even after a week or ten days some cells are destined to produce skin, others neurons, others cells in the digestive system, and so on. This process of specialization is accomplished by turning off all the genes in a cell’s DNA except those needed to perform its particular function. Thus, most of the genes in any adult cell are turned off.
For the first half-dozen divisions of the fertilized egg, however, no genes in some of these cells are turned off, so each such cell has the potential to develop into any of the specialized cells eventually present in the adult. These cells are called embryonic stem cells. As the organism develops, a series of intermediate stem cells are formed. The many types of cells that appear in the skin, for example, come from stem cells that can develop into any of these types, but not into muscle or nerve tissue. These cells are called somatic stem cells.
The great hope of a new field called regenerative medicine is that an individual’s stem cells can be used to engineer to create organs that can be transplanted—new heart muscle or nerves, for example. Such organs would contain the individual’s own DNA and would therefore not be rejected by his or her immune system. To realize this dream, however, scientists will need to have access to stem cells in which all of the genes are turned on, so that the cells can be guided into the entire final state.
One way to obtain such cells would be to create a cloned embryo with the patient as the DNA donor and then harvest the stem cells from the embryo. This approach has several problems. For one thing, it would require a large supply of human ova, which would have to be removed surgically from healthy women. For another, in the United States the use of embryonic stem cells is mired in the national debate over abortion and hence encounters political problems.
Fortunately, in 2007 researchers in the United States and Japan developed ways to produce stem cells without recourse to an embryo. By using viruses to inject genes into the DNA of a normal skin cell, they could reset the switches that turn genes off, just as the egg does in the cloning process. The result is that we can produce stem cells by direct manipulation of a cell’s DNA, without recourse to cloning at all. Thus, there is hope that regenerative medicine can move forward without the restraints of the political and practical problems discussed above.
CHAPTER EIGHTEEN
Evolution
IF YOU OR YOUR CHILDREN went to public school in the United States, chances are that creationism—the biblical account of human origins—wasn’t a part of the science curriculum. This educational decision was not a foregone conclusion. A dedicated group of scientists has been fighting a series of pitched legal battles in courtrooms across the country—in Arkansas, in California, in Pennsylvania—to protect science from what many of us see as one of the greatest threats to the science education of America’s children.
This chapter will offend some people, but that is nothing new. The theory of evolution has been offending people for more than a century. Two strongly held views about the origin of our planet and its life are in severe disagreement. Biblical creationists accept on faith the literal Old Testament account of creation. Their beliefs may include (1) a young Earth, perhaps less than 10,000 years old; (2) catastrophes, especially a worldwide flood, as the origin of Earth’s present form, including mountains, canyons, oceans, and continents; and (3) miraculous creation of all living things, including humans, in essentially their modern forms. If you are a creationist, the Bible—not nature—dictates what you believe. Creationists subordinate observational evidence to doctrine based on their interpretation of sacred texts. The tenets of biblical creationism are not testable, nor are they subject to dramatic change based on new data. In other words, creationism is a form of religion.
The testimony of nature—evidence that anyone can observe and interpret—belies creationist dogma. If Earth is only 10,000 years old, how could the Grand Canyon have been carved a mile deep in solid rock? How could plate tectonics split apart Europe and North America with spreading rates of only a few inches per year? How could radiometric age dating, based on the steady decay of radioactive elements, give ages of hundreds or thousands of millions of years for most rocks? How could seasonally varying deposits of Mississippi River sediments, coral reefs, and deep ocean deposits contain hundreds of thousands of annual layers, all on top of much older rocks? Nature has much to tell us about our origins, if only we listen without prejudice.
The biblical story of creation has great poetic beauty and metaphorical power. The biblical story of creation (religion) and the theory of evolution (science) are different, complementary ways of answering questions about the origins of life and humans. Because of this fundamental difference, we believe that it is inappropriate to incorporate creationism into any science curriculum.
The scientific theory of evolution has been developed and modified, challenged and tested, over centuries of geological and biological observations. The theory of evolution has led to countless specific predictions regarding location of fossils, age of rock formations, and genetic similarities of different species. Evolution is testable and, like any scientific theory, subject to change based on new data. The central idea that has emerged from these studies is:
All forms of life evolved by natural selection.
One must distinguish between the fact of evolution and any particular theory of evolution, a distinction that will be clear if you think about gravity. There have been many theories of gravity, from Newton to Einstein to (perhaps) a fully unified field theory Any one of these theories may be wrong, incomplete, or incorporated into another. But if you drop an object, it falls, regardless of which theory you believe. That
is the fact of gravity.
In the same way, the fossil record, molecular biology, and geological research all buttress the notion that modern complex life on Earth evolved out of earlier, simpler forms. This is the fact of evolution. As with gravity, there are different theories of evolution that purport to describe this process. Any of them, starting with Darwin’s, may be wrong or incomplete. The correctness or incorrectness of any particular theory, however, doesn’t change the fact of evolution, any more than one can question the fact of gravity.
Most scientists agree about one aspect of evolution. Life seems to have arisen in a two-step process. The first stage—chemical evolution—encompasses the origin of life from nonlife. Once life appeared, the second stage—biological evolution—took over.
CHEMICAL EVOLUTION
On a clear winter’s night, gazing into the cold depth of the sky, you can face the brute fact that the universe is a cold, hostile, forbidding place, almost completely devoid of havens for living things. That life should evolve at all is a remarkable thing, requiring just the right temperature, pressure, and chemical elements, as well as a source of energy to combine those elements. The early Earth provided all those conditions.
The first requirement for the evolution of life as we know it is an ocean, the mixing bowl for the chemicals of life. The early Earth had both an abundance of water and temperatures that remained within the rather narrow range of freezing and boiling water. Within a few million years of Earth’s solidification, water covered most of the globe’s surface.
Life’s origins also required an abundant supply of at least four key elements: carbon, hydrogen, nitrogen, and oxygen. All of these components were present in the early atmosphere, which was very different from the air we now breathe. The gases that came from volcanoes to form the first atmosphere were a mixture of nitrogen (N2), carbon dioxide (CO2), and water (H2O), perhaps with a bit of hydrogen (H2), methane (CH4), and ammonia (NH3) tossed in. These gases mixed with the wave-tossed surface layers of the early ocean, which thus contained all the essential elements of life.
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