Designer Genes: A New Era in the Evolution of Manby Steven Potter
This compelling new book covers the most important revolution since Darwin how cutting-edge genetic science will soon allow us to speed up and transform our own evolution, and the moral choices we must make as we improve, alter, and even duplicate ourselves. The fact is that, until now, human evolution has been exceedingly slow. But there's about to be a profound
This compelling new book covers the most important revolution since Darwin how cutting-edge genetic science will soon allow us to speed up and transform our own evolution, and the moral choices we must make as we improve, alter, and even duplicate ourselves. The fact is that, until now, human evolution has been exceedingly slow. But there's about to be a profound change in this process, with a perfect storm of revolutions in the fields of genetic modification, stem cells, DNA sequencing, and embryo manipulation. The result is that it will soon be possible for parents to consciously choose the genes of their children, defining their intelligence, appearance, athletic ability, and health. The ramifications could be enormous, with each generation smarter, more technologically proficient, and better able to design the genes of their offspring. Where will this evolution on steroids take us? Designer Genes presents a balanced view, describing the underlying science in accessible terms and discussing the pros and cons of implementing this new technology. A leading expert in the field, Steven Potter covers a broad range of topics on this challenging subject, presenting fascinating details of case histories and ongoing discoveries: the true story of Adam, who as an early embryo was genetically selected to save his sickly sister the surprising human genome and DNA sequence comparisons across species dogs, an informative example of human-driven evolution the sequencing revolution, with the price of determining a person's complete DNA sequence becoming much more affordable genetic diseases and what is being discovered about them every day stem cells and their almost magical powers Designer Genes also investigates such controversial questions as: When is an embryo a person? Are we smart enough to pick optimal gene combinations? What will the government's role be? Science has brought us an astonishing understanding of the genetic ba
“Potter makes clear that understanding what genetic research entails as well as the bioethics involved is necessary for participating in public discourse and politics. Therefore, Potter’s thorough approach is to be lauded, and recommended to readers curious about this important subject, and those more urgently seeking their own genetic answers.” – Booklist
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Designer GenesA New Era in the Evolution of Man
By Steven Potter
Random HouseCopyright © 2010 Steven Potter
All right reserved.
The True Story of Adam
Both Lisa and Jack Nash were carriers for a Fanconi anemia gene mutation. They didn't know it, because they were quite healthy, but they both had one good and one bad (nonfunctional) copy of this gene. Their first child, Molly, unfortunately received two bad copies of the gene, one from each parent. As a result, she had Fanconi anemia, which is a disease with several manifestations, but the most lethal is a blood disorder: the body fails to produce enough blood cells.
Molly was born on July 4, 1994, and it was clear from the outset that things weren't right. As Lisa held her newborn daughter in her arms she knew there was a problem. Instead of a forceful cry there was but a whimper. And her thumbs were missing! Lisa quickly asked for a copy of a book, David Smith's Recognizable Patterns of Human Malformation. She had worked for years in a hospital as a nurse for newborns and knew that this was the standard reference book for birth defects. It lists diseases according to symptoms. Using this book Lisa was the first to diagnose her daughter with the very rare Fanconi anemia. Molly suffered from a severe case that would end her life in a few years unless a transplant could be performed. Donor bone marrow from an adult or an umbilical cord from a newborn would have blood stem cells capable of restoring her ability to make blood. But the donor cells must be well matched to those of Molly. Otherwise the donor cells would probably recognize Molly's cells as foreign, like bacteria, and launch a lethal rejection of her body. The transplanted blood cells, meant to save her, would then actually kill her. And despite an extensive search no compatible donor could be found.
Desperate to save their daughter, Lisa and Jack considered their options. If they risked going ahead with a bone-marrow transplant from a nonrelative donor that wasn't well matched, the chances of success were slim, below one in five. Doing nothing would result in Molly's certain death. At this point there didn't seem to be any other options. But then, as they thought more, they decided perhaps there was another choice. If they had another child, they might be lucky, and it might not suffer from Fanconi anemia (only 25 percent of their children would be unfortunate enough to receive two bad copies of the gene). But the odds were still poor that any additional child would provide a compatible transplant match for Molly.
They decided to go with a modified version of this option, very radical at the time. Indeed, they would be the first. They would take chance out of the equation. They would definitely have another child, but they would use the latest scientific advances to be certain that this child would not have Fanconi anemia, and that it would be compatible with Molly, and would therefore be able to save Molly's life.
The procedure was a modern-day variant of in vitro fertilization (IVF), which has been around for decades. Louise Brown, born in 1978, was the first child conceived through IVF. The procedure is remarkably simple in concept-eggs are mixed with sperm in a test tube, thereby achieving fertilization. The fertilized eggs, or zygotes, are grown for a brief period in the laboratory, and then surgically inserted into the mother, where they implant themselves into the wall of the uterus and develop into normal babies. This procedure has been enormously successful in helping otherwise infertile couples conceive. Approximately 1 percent of all babies now born in the United States are the result of IVF.
For the Nash family, however, another step was required, to make sure that the baby carried the correct combination of genes to provide a good transplant match with Molly. Eggs from Lisa Nash were mixed with sperm from Jack Nash, using normal IVF procedures to make fifteen early embryos. Three days after fertilization, when the embryos were at the eight-cell stage, a single cell was removed from each and used for genetic diagnostics, which didn't harm the embryos at all. The cells were analyzed for mutation of the Fanconi anemia gene, and for transplant match determination. An embryo with the correct gene combination was then transferred into the uterus of Lisa Nash. The result was the birth of a healthy boy whose umbilical cord blood stem cells provided a transplant that saved Molly's life. They had cured their precious daughter! And in the process they had acquired a healthy son, of course to be loved and cherished as well.
In a very prescient decision, the Nashes decided to name their new child Adam. The name acknowledges that Adam Nash, like the biblical Adam, represents the first of a new breed. Preimplantation genetic diagnosis, or PGD, is now performed routinely at many centers around the world. Single cells are removed from early embryos to determine their genetic makeup. It is almost exclusively used, at present, for the identification of embryos that are free of genetic disease carried by their parents. These centers all strongly insist that they are not involved in the production of designer babies, but rather the generation of healthy babies, lacking a deadly gene combination that would otherwise doom them to disease.
But the principle is established. The methodology of creating a batch of embryos and applying a genetic screen to determine which will be used is now entrenched. Currently we focus on the absence of gene variants known to cause disease. But we are on the verge of an incredible explosion of understanding of the functions of different forms of genes. In the future we will be able to completely sequence the DNA of each embryo, and to see what version of each gene is present. It will then be possible to add a large number of factors to the selection formula. Instead of just looking for absence of the Fanconi anemia gene, for example, it will be possible to choose on the basis of intelligence, musical talent, height, body build, mental health, eye color, hair color, and a host of other characteristics.
But this strategy of testing a small set of embryos-approximately ten to twenty are usually produced-is limited in its potential, because the desired gene combinations might not be found. Two new technologies offer even more sweeping possibilities. First, developments in the stem-cell field could make it possible to generate thousands of embryos to screen, instead of just ten to twenty. The ideal gene mixture will be much more likely to occur in a large group of embryos than in a small one. The second technology goes a giant step further, allowing one to take a single embryo and to modify its genes at will. The Nobel Prize in Medicine in 2007 was awarded to Mario Capecchi, Sir Martin Evans, and Oliver Smithies for the research leading to this breakthrough, which is routinely used today in research laboratories for the genetic modification of mice.
Our children are our biggest investment. They are what remain of us in the future. We want them to be the best that they can be. Our desires and our technologies have combined to place us on the proverbial slippery slope. It is not clear that we can change course now. The timing of the travel is subject to debate. Will it be five, ten, or fifty years? But the path we are following is apparent. And what is the final destination? Where is humanity headed?
Figuring Out Which Genes Do What
Before we can make children with chosen sets of gene combinations to produce desired characteristics, we first have to figure out which genes do what. Right now we don't know. We are relatively ignorant of the gene type blends that would make a person smarter, stronger, and healthier. But, once again, there is a technological revolution under way that will rapidly change this.
To appreciate the revolution we must first review some underlying principles. This is a complex area that molecular biologists have been working for many decades to better understand. Nevertheless, the basics are surprisingly straightforward.
So, what are genes anyway? What do they do? You might think of genes as little computer programs, each designed to have a specific function. Maybe one gene has a contraction function and contributes to muscle contraction, while another might help the neurons of the brain communicate with one another. And just like a computer, which can have many programs but might only have a few in use at a given time, a cell has many genes, but only a fraction will be active at once. Every cell in your body has the same set of genes, but different cell types use different combinations of genes. And even a single cell will change the set of genes it is using with time, according to need.
How do genes do their work? Actually, genes don't really do the work themselves, they tell others to do it. The genes are just the information storehouse. Genes are made of DNA, and the DNA consists of strings of bases, called A, T, G, and C in molecular biology shorthand. James Watson, Francis Crick, and Maurice Wilkins shared a Nobel Prize in 1962 for their work defining the elegant double-helix structure of DNA. Just as a computer uses a binary code of ones and zeros, the human cell uses a quaternary code of these four bases. The sequence of the bases of the DNA provides the information. The DNA is like the hard drive.
But how does this information get used? As shown in the diagram on the next page, DNA is used to make ribonucleic acid (RNA), which is used to make proteins. The proteins, then, are the workers. Proteins have many different functions. Proteins in muscles allow the muscles to contract. Enzymes are proteins, and among other things, they catalyze the biochemical reactions that turn food into energy. Proteins in the surface membranes of the cell are like little eyes and ears, and allow the cell to sense its surroundings. Some proteins are secreted from a cell and float away to nearby cells, communicating with them. The messages received at the outer surface of the cell must be carried to the DNA-containing nucleus, again by proteins, where the cell can make appropriate changes in the way it activates its genes in response. Indeed, proteins do almost everything in the cell that needs to be done.
It is interesting to note that not only are proteins the products of genes, but they also facilitate the process of gene expression. The protein RNA polymerase makes the RNA copy of DNA. This is called transcription, because it is just copying, or transcribing, the base sequence of the DNA into the base sequence of the RNA. The resulting RNA, called messenger RNA, or mRNA for short, serves a courier function, carrying the sequence information from the nucleus, where the DNA resides, out to the cytoplasm of the cell, where protein is made. In the cytoplasm there are machines, called ribosomes, made up of many dozens of proteins, which have the job of translating the base sequence arriving in the mRNA into the subunit sequence of newly synthesized protein. There is circularity in the process, with many proteins necessary to activate, or express, a gene, which in turn makes more protein.
Many of the molecules of the body are polymers, made by joining a large number of building blocks together. DNA, as mentioned earlier, is a double helix made up of the four bases A, T, G, and C. The closely related RNA also has four bases, A, U, G, and C, with a U in place of the T in DNA. And proteins are made up of subunits called amino acids, which have different physical properties that give them different functions. Everyone has heard of protein as a part of the food we eat. When we digest this protein we break it down into the subunits, the amino acids, and then our cells use these amino-acid building blocks to synthesize their own proteins.
There are twenty different amino acids, almost the same number as there are different letters in our alphabet, and each protein is on average a few hundred amino acids long. This allows an enormous variety of proteins to be made. Imagine how many different words you could make if each word was a few hundred letters long, and if the change of even a single letter in the word could dramatically change its meaning. This is exactly the situation for proteins. In many cases the change of even a single amino acid can make the difference between life and death.
An important principle in molecular biology is the complementarity of bases. Watson and Crick showed that in double-stranded DNA the base A is always opposite the base T, and the bases G and C are also always found across from each other. It turns out that an A "fits" next to a T, and loosely binds with it, and the same is true for the base pair G and C. When DNA is replicated the two strands are pulled apart, and each strand is used to make a complementary strand, restoring the double stranded structure and giving two DNA copies in place of the original one. Proteins, including DNA polymerase, also carry out this DNA replication, using the principle of base complementarity to make sure that the newly synthesized strands of DNA have the correct sequence. Again, an A in one strand is always placed next to a T in the other, and a G next to a C. A single round of DNA replication must take place before a cell divides, so the two daughter cells can each receive a complete copy of the DNA.
RNA polymerase also uses this principle of base complementarity when it takes one of the strands of DNA and transcribes an RNA copy from it. But, as we've mentioned, RNA is not exactly the same as DNA. When RNA is being made the RNA base U will go next to the DNA base A. The diagram below shows one strand of DNA, called the coding strand because it encodes protein, being transcribed into RNA.
You might wonder how the base sequence of DNA is used to determine the amino-acid sequence of protein. There are only four bases, but twenty amino acids, so clearly there is not a one-to-one correspondence. Cracking the genetic code was one of the major early accomplishments of molecular biologists. It took many years and a great deal of ingenious experimentation to understand this process. It turns out that three bases are needed to encode, or specify, each amino acid. Each base triplet encoding a single amino acid is called a codon. For example, the codon ATG encodes the amino acid methionine, abbreviated "met." Another three bases will encode a different amino acid, and so on. A gene, therefore, consists of DNA, which is a chain of bases, with each sequential codon of three bases specifying a particular amino acid of the encoded protein. Different genes have different base sequences, and therefore encode different proteins with different roles.
Excerpted from Designer Genes by Steven Potter Copyright © 2010 by Steven Potter. Excerpted by permission.
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Meet the Author
Steven Potter was an undergraduate at UCLA, received his Ph.D. from the University of North Carolina at Chapel Hill, and was a Postdoctoral Research Fellow at Harvard Medical School. He is currently a professor in the Department of Pediatrics, Division of Developmental Biology, at Children’s Hospital Medical Center in Cincinnati. Potter has published over a hundred research papers, including more than a dozen in the prestigious journals Nature, Cell, and Science. He also co-authored the third edition of the medical school textbook Larsen’s Human Embryology and serves on the editorial boards of the science journals Transgenics and Developmental Biology. His research has covered a wide range of topics, including evolution, jumping genes, targeted modification of genes, and the study of how organs form.
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