Science Matters

by Robert M. Hazen

  The Universal Code

  Just as a simple alphabet can be used to form a large number of words, a simple genetic code can produce a wide variety of living things. You are different from a blade of grass or an orangutan because the sequence of bases in your DNA is different from the sequence in theirs. The basic processes described above, however, operate alike in you and all other living things.

  Scientists now see the gene, whose existence was postulated by Mendel, as a specific segment of a much longer DNA molecule. Genes are the sentences in our genetic book. Different organisms have different numbers of genes (humans have about 25,000 for example, and a simple bacterium might have 1,000), and many genes can fit along a single molecule of DNA. A single gene may involve anything from a few dozen to a few thousand base pairs, depending on the size of the protein to be made.

  Flu Bugs and Other Viruses

  The virus is either the simplest living system or the most complex nonliving one, depending on your definitions. Unlike a cell, which is highly structured, the virus simply consists of a core of nucleic acid wrapped in a protein coating. A virus may have only a few genes coded in its nucleic acid and only a few different proteins in its coat. But if a receptor in a cell’s outer membrane recognizes one of those outer proteins, the virus can fool the cell into opening the door.

  Once inside, the virus appropriates the cell’s machinery to produce more viruses. The DNA or RNA nucleic acid in viruses is coded to reproduce itself and its proteins. Once released inside the cell, this RNA pushes the cell’s own mRNA aside and starts to direct the synthesis machinery. When the resources of the cell have been plundered to produce many new viruses, the cell dies and the viruses are released to repeat the cycle.

  Some viruses contain strands of RNA and enzymes that allow those strands to be converted into DNA and inserted into the cell’s own genetic code. This action can disrupt the smooth workings of a cell, and thus threaten the entire organism. One of these so-called retroviruses is responsible for AIDS.

  Unlike the DNA in your cells, which is constantly being checked and repaired for any unwanted changes, viral DNA and RNA have the unfortunate ability to mutate rapidly. Consequently, viral diseases constantly evolve. That’s why new viral diseases seem to pop up every few years, and the flu vaccine you took this year may have little effect on next year’s strain.

  SEX—A GOOD IDEA

  Your cells’ genetic machinery is designed to make exact copies of the coded message, so why isn’t every human exactly the same? Why don’t we all have exactly the same appearance, the same strengths and weaknesses? The answer is sex.

  Chromosomes

  DNA does not just float around loose in the cell’s nucleus. It is stored in structures called chromosomes, which consist of one long double helix of DNA wrapped around a core of proteins. Chromosomes are something like thread around a spool, but with a single strand of DNA being wrapped sequentially around many adjacent small spools. Different species have different numbers of chromosomes: humans weigh in with 46 (23 pairs), while mosquitoes have only 6, and goldfish have 94.

  In many situations cells reproduce by themselves—asexually This happens when you get a cut that heals, when a plant grows, or when pond scum spreads during warm summer months.

  The division of a single cell into two identical daughters is called mitosis. This complex process is easy to describe but hard to understand in detail. Mitosis begins when the chromosomes replicate themselves, each length of DNA splitting in half and copying itself. The resulting replicate chromosomes join together and look like the letter X when viewed through a microscope.

  At this point a network of proteins (called spindles) forms in the cell and the matched pairs of chromosomes split up, one being pulled to each pole of the cell. This separation complete, another band of proteins forms around the cell’s equator and squeezes down, separating it into two halves, each of which has a full complement of chromosomes. The end result of mitosis: two cells, each with identical genetic codes, where only one existed before.

  Cells in your body are constantly dividing, and different cells have different cycle times—those in the intestinal walls divide every day, those in the skin every few weeks, for example. Only cells in the nervous system seem to stop dividing at adulthood.

  Meiosis—Reproduction with Sex

  In humans and other organisms that reproduce sexually, each parent contributes one chromosome to each pair. This simple fact has two important consequences. First, it means that each offspring is similar to but different from both parents. Second, it means that the pairing of chromosomes provides the mysterious mechanism that Mendel first discovered in his garden of pea plants. Each gene is one sequence of bases along the double helix of DNA that makes up either the mother’s or the father’s contribution to a chromosome pair. The unit of heredity is part of a physical molecule transferred from parents to offspring.

  While the goal of mitosis is to produce a daughter cell that is identical to the parent, reproduction of organisms (as opposed to cells) has a somewhat different goal. If each parent contributes half of the genes to the offspring and the number of the offspring’s genes must remain the same, then there must be a mechanism for producing a daughter cell with half the number of chromosomes of the original.

  The process of cell division that begins with a cell with a full complement of chromosomes and ends with cells with half this complement is called meiosis. Meiosis occurs only in certain specialized cells in the reproductive system. In its initial stages, meiosis is identical to mitosis—the chromosomes replicate themselves. At this stage the cell undergoing meiosis has exact copies of the organism’s original chromosomes, half of which were contributed by the father and half contributed by the mother. But then, instead of just splitting up (as in mitosis), the pairs begin to swap segments of DNA to produce completely new chromosomes, each with a mixture of DNA from both parents. These new chromosome pairs are separated. The result: the chromosomes are grouped in the four quadrants of the cell, and each group has exactly half the number of chromosomes in an ordinary cell. The cell then divides four ways, producing four cells, each containing a group of brand-new chromosomes with shuffled DNA. Thus does meiosis produce the male’s sperm and the female’s ova.

  The first step in the production of a new organism is fertilization, the union of the ovum and sperm of the two parents. We are used to thinking of fertilization in human, or at least mammalian, terms, but the same things happen in plants, where ordinary pollen is the sperm. Fertilization produces a single cell, the zygote, with a full complement of chromosomes—one chromosome in each pair coming from the sperm, the other from the ovum. This process on the cellular level explains Mendel’s notion that an offspring receives its genetic endowment half from the mother, half from the father.

  Does Life Begin at Conception?

  The question of whether life begins at conception comes up constantly in the debate over abortion rights in the United States. This is not a scientific question, but a legal, moral, and ethical one. It illustrates an important point about what science can and cannot do. Science is very good at answering quantitative questions about how the universe works, but cannot provide answers to some important questions about how we should behave as individuals or as a society.

  A scientist can tell you the following facts:

  At the moment of conception, two strands of DNA come together in a combination that never existed before.

  Each of these two DNA strands existed previously in parent organisms and were themselves the result of a unique pairing. This process probably extends back billions of years.

  The new combination is incapable of independent existence for months after conception, and is entirely dependent on the mother during that time.

  Whether life begins at, before, or after fertilization is not something that a scientist can answer as a scientist, although he or she may well have a deeply held opinion based on philosophical or religious arguments.

&nbs
p; New Reproductive Technologies

  New technologies offer hope for would-be parents who are unable to conceive. Many couples are infertile because of mechanical defects in their reproductive system. If both parents produce viable sex cells and the mother’s uterus is healthy, however, the eggs and sperm can be combined outside of the mother. Fertilization can take place in a test tube—in vitro (literally, inside the glass), to use the jargon of biologists. The fertilized egg, a living human embryo, is then implanted in the mother and pregnancy proceeds normally.

  As reproductive biologists learn more about how to induce and control fertilization, troublesome ethical and legal questions arise. Several eggs are usually fertilized at once, and most of those embryos are frozen and stored. If a couple divorces, who has the legal rights to frozen embryos? New techniques allow physicians to identify the sex and genetic traits of test tube embryos before implantation. What are justifiable genetic criteria for rejecting a viable embryo? If the biological mother is unable to bear children, a surrogate mother may grow and nurture the embryo. What are the rights of the surrogate mother? Zoo biologists have successfully bred rare species by using surrogate mothers of a different species. Where do we draw the line with human embryos?

  FRONTIERS

  The Human Genome Project

  The past few years have seen numerous news stories on the Human Genome Project, the first multibillion-dollar basic research enterprise in the life sciences. The most highly publicized goal of the project was the base pair by base pair mapping of the entire three-billion-letter sequence of the human genetic code. The first draft of this sequence was celebrated with a White House ceremony in 2000, and the final task was completed in 2005. The results contained a number of surprises. For example, given the length of the human genome, most biologists estimated that we have about 100,000 genes, each coding for a different protein. It turns out that the actual number is closer to 25,000 genes, and most of our genetic makeup (by some estimates 95 percent!) does not code for proteins. A wide variety of functions have been ascribed to this “junk DNA.” Some of it doubtlessly turns genes on and off, some represents genes that are no longer used and are in the process of disappearing, and some may have no function at all. Working out what the genome means will be a major task of twenty-first-century science.

  As sequencing technologies have become much faster and cheaper, the genome project has been extended to numerous other organisms, including mice, dogs, rabbits, chimpanzees, fish, plants, yeast, and hundreds of microbial species (especially those that cause diseases). Each new completed genome reveals striking similarities, as well as important differences, among all living things.

  Gene Regulation and Differentiation

  Every cell in your body (except for the sex cells) contains exactly the same DNA, and therefore exactly the same genes. Yet not every cell performs the same function. For example, each cell contains the code for making insulin, but only a relatively small number of cells in the pancreas actually do so. Most genes in a cell are not used. The mystery of how genes are turned on and off (or regulated) remains an area of intense research today.

  The solution to this problem may be partly related to all that junk DNA. Could some of the DNA that doesn’t code for genes play a role in turning genes on and off? Could some of that DNA make short strands of micro-RNA that act like molecular switches (called riboswitches)? If this is true, then junk DNA may well turn out to be just as interesting as genes.

  Another problem closely associated with that of gene regulation involves the question of how complex organisms develop from a single cell. All the cells in your body arose from a single cell, but all are now very different and could not be turned into one another. Cell differentiation is one of the main concerns of embryology. It appears that DNA doesn’t code only for proteins and regulation, but also contains instructions that turn genes on and off depending on how cells are developing elsewhere in an organism. Biologists have just started to scratch the surface of this complex problem, and we will not have a complete understanding of molecular genetics until gene regulation and cell differentiation are understood.

  CHAPTER SEVENTEEN

  Biotechnology

  THE TWENTIETH CENTURY, with the advent of the Internet, nuclear energy, and the internal combustion engine, has been described as the century of physics. If we accept this label, then there is little doubt that our current era will be the century of biology. In fact, we can already see the vague outlines of what new biotechnologies will bring us.

  In the nineteenth century, scientists discovered a central fact about living systems—they are based on chemistry. When we say that something is alive, in other words, we are saying that it is running certain types of chemical reactions. In the twentieth century we discovered that life’s chemistry is based on DNA, as discussed in Chapter 16. Today we are engaged in a massive project to understand the details of how that chemistry works, and as always happens when new areas of knowledge open up, when we are able to “get under the hood” of living systems, new kinds of technologies become possible. Just as life in the year 2000 would have been almost incomprehensible to someone living in 1900, we cannot even begin to imagine the life that our descendants at the end of this century will lead.

  The basic scientific ideas behind all of these technologies, already introduced in Chapters 15 and 16, are that:

  All life is based on the same chemistry

  and genetic code.

  In this chapter we will talk about some of the directions that this realization is taking us in right now.

  DNA FINGERPRINTING

  The idea that someone can be unambiguously identified by his or her DNA is well established today, reinforced by countless television police dramas. And it is a fact that each person’s genome is different from every other person’s and can therefore be used (in principle) as a unique identification.

  The catch is that sequencing an entire genome for even one person is still an extremely expensive and time-consuming process. And although the cost of sequencing a genome is falling, it will be decades before the cost drops to the point that the process will be cheap enough to be used in the courts. Consequently, the alternative approach of DNA fingerprinting is used. Instead of looking at the whole genome, scientists look at specific genetic landmarks and use them for identification. Think of this process as being analogous to seeing the Eiffel Tower and knowing that you’re in Paris, without having to have a street map of the entire city.

  Two different sets of genetic landmarks are now used—one in an old method that has been widely accepted in the courts, the other in a new method that is being developed in the laboratory. We’ll talk about them separately.

  VNTR

  As we pointed out in Chapter 16, only a small portion of human DNA actually codes for proteins. Much of the rest seems to be a jumble of base pairs, some representing genes that are no longer used, some regulating when genes are turned on and off, but most of unknown origin and purpose. In the latter category is a structure known as a variable number tandem repeat, or VNTR. These features are repeating sequences of nonsense DNA located at specific places along the genome. Finding a VNTR in a genome is something like reading a sentence and yabadayabadayabada suddenly some nonsense letters appear before the text resumes. The number of repeats varies from place to place in a single genome and from person to person at a specific location in the DNA. The number of repeats can vary from a few to about 250.

  VNTRs are used as landmarks in DNA fingerprinting. The basic idea is that the number of repeats at a specific location varies from one person to the next, and so can be used to identify a specific individual. The procedure used to compare two strands of DNA works like this: Molecules called restriction enzymes are used to cut the DNA at a specific point on both sides of a VNTR. In general, because the number of repeats varies from one person to the next, this procedure will result in two DNA pieces of different lengths for segments taken from the corresponding spots on DNA from differe
nt individuals. A small molecule containing a radioactive nucleus is attached to each DNA strand; the strands are then placed in a gel and an electric field is applied. The field causes the strands to move, with the shorter strand moving faster than the longer one. After a specific amount of time, the field is turned off and a photographic film is laid on top of the system. When the radioactive atoms decay, the film is exposed and the position of the DNA strands detected.

  If the two strands are of the same length (as they would be if they came from the same individual), the dark marks on the film will be at the same place, whereas if they are not of the same length they will be at different places. If this process is repeated for several different VNTRs for a given individual, the result will be a kind of bar code, with each bar corresponding to a different VNTR. This bar code, then, becomes the basis for identifying the DNA.

  To interpret the results of this sort of test, you have to realize that the chances of any specific VNTR having the same number of repeats in two people is about 1 in 250. In other words, if we look at only one location on the DNA, two people in a large auditorium can be expected to match just by chance. In practice, DNA fingerprinting is done by using five or more locations, a procedure that reduces the probability of a chance match to less than one in a trillion. DNA identification using the VNTR technique is so well developed that it is widely used in criminal investigations, in the identification of bodies in disaster situations, and in establishing paternity.