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More Than Human: Embracing the Promise of Biological Enhancement

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More Than Human: Embracing the Promise of Biological Enhancement Cover

 

 

Excerpt

CHAPTER 1

Choosing Our Bodies

In 1989, Raj and Van DeSilva were desperate. Their daughter Ashanti, just four, was dying. She was born with a crippled immune system, a consequence of a problem in her genes.

Every human being has around thirty thousand genes. In fact, we have two copies of each of those genes--one inherited from our mother, the other from our father. Our genes tell our cells what proteins to make, and when. Each protein is a tiny molecular machine. Every cell in your body is built out of millions of these little machines, working together in precise ways. Proteins break down food, ferry energy to the right places, and form scaffoldings that maintain cell health and structure. Some proteins synthesize messenger molecules to pass signals in the brain, and other proteins form receptors to receive those signals. Even the machines inside each of your cells that build new proteins?called ribosomes?are themselves made up of other proteins.

Ashanti DeSilva inherited two broken copies of the gene that contains the instructions for manufacturing a protein called adenoside deaminase (ADA). If she had had just one broken copy, she would have been fine. The other copy of the gene would have made up the difference. With two broken copies, her body didn?t have the right instructions to manufacture ADA at all.

ADA plays a crucial role in our resistance to disease. Without it, special white blood cells called T cells die off. Without T cells, ADA-deficient children are wide open to the attacks of viruses and bacteria. These children have what?s called severe combined immune deficiency (SCID) disorder, more commonly known as bubble boy disease.

To a person with a weak immune system, the outside world is threatening. Everyone you touch, share a glass with, or share the same air with is a potential source of dangerous pathogens. Lacking the ability to defend herself, Ashanti was largely confined to her home.

The standard treatment for ADA deficiency is frequent injections of PEG-ADA, a synthetic form of the ADA enzyme. PEG-ADA can mean the difference between life and death for an ADA-deficient child. Unfortunately, although it usually produces a rapid improvement when first used, children tend to respond less and less to the drug each time they receive a dose. Ashanti DeSilva started receiving PEG-ADA injections at the age of two, and initially she responded well. Her T-cell count rose sharply and she developed some resistance to disease. But by the age of four, she was slipping away, no longer responding strongly to her injections. If she was to live, she?d need something more than PEG-ADA. The only other option at the time, a bone-marrow transplant, was ruled out by the lack of matching donors.

In early 1990, while Ashanti?s parents were searching frantically for help, French Anderson, a geneticist at the National Institutes of Health, was seeking permission to perform the first gene-therapy trials on humans. Anderson, an intense fifth-degree blackbelt in tae kwon do and respected researcher in the field of genetics, wanted to show that he could treat genetic diseases caused by faulty copies of genes by inserting new, working copies of the same gene.

Scientists had already shown that it was possible to insert new genes into plants and animals. Genetic engineering got its start in 1972, when geneticists Stanley Cohen and Herbert Boyer first met at a scientific conference in Hawaii on plasmids, small circular loops of extra chromosomal DNA in which bacteria carry their genes. Cohen, then a professor at Stanford, had been working on ways to insert new plasmids into bacteria. Researchers in Boyer?s lab at the University of California in San Francisco had recently discovered restriction enzymes, molecular tools that could be used to slice and dice DNA at specific points.

Over hot pastrami and corned-beef sandwiches, the two Californian researchers concluded that their technologies complemented one another. Boyer?s restriction enzymes could isolate specific genes, and Cohen?s techniques could then deliver them to bacteria. Using both techniques researchers could alter the genes of bacteria. In 1973, just four months after meeting each other, Cohen and Boyer inserted a new gene into the Escherichia coli bacterium (a regular resident of the human intestine).

For the first time, humans were tinkering directly with the genes of another species. The field of genetic engineering was born. Boyer would go on to found Genentech, the world?s first biotechnology company. Cohen would go on to win the Nobel Prize in 1986 for his work on cell growth factors.

Building on Cohen and Boyer?s work with bacteria, hundreds of scientists went on to find ways to insert new genes into plants and animals. The hard work of genetically engineering these higher organisms lies in getting the new gene into the cells. To do this, one needs a gene vector?a way to get the gene to the right place. Most researchers use gene vectors provided by nature: viruses. In some ways, viruses are an ideal tool for ferrying genes into a cell, because penetrating cell walls is already one of their main abilities. Viruses are cellular parasites. Unlike plant or animal cells, or even bacteria, viruses can?t reproduce themselves. Instead, they penetrate cells and implant their viral genes; these genes then instruct the cell to make more of the virus, one protein at a time.

Early genetic engineers realized that they could use viruses to deliver whatever genes they wanted. Instead of delivering the genes to create more virus, a virus could be modified to deliver a different gene chosen by a scientist. Modified viruses were pressed into service as genetic ?trucks,? carrying a payload of genes loaded onto them by researchers; these viruses don?t spread from cell to cell, because they don?t carry the genes necessary for the cell to make new copies of the virus.

By the late 1980s, researchers had used this technique to alter the genes of dozens of species of plants and animals?tobacco plants that glow, tomatoes that could survive freezing, corn resistant to pesticides. French Anderson and his colleagues reasoned that one could do the same in a human being. Given a patient who lacked a gene crucial to health, one ought to be able to give that person copies of the missing gene. This is what Anderson proposed to do for Ashanti.

Starting in June of 1988, Anderson?s proposed clinical protocols, or treatment plans, went through intense scrutiny and generated more than a little hostility. His first protocol was reviewed by both the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). Over a period of seven months, seven regulatory committees conducted fifteen meetings and twenty hours of public hearings to assess the proposal.

In early 1990, Anderson and his collaborators received the final approval from the NIH?s Recombinant DNA Advisory Committee and had cleared all legal hurdles. By spring, they had identified Ashanti as a potential patient. Would her parents consent to an experimental treatment? Of course there were risks to the therapy, yet without it Ashanti would face a life of seclusion and probably death in the next few years. Given these odds, her parents opted to try the therapy. As Raj DeSilva told the Houston Chronicle, ?What choice did we have??

Ashanti and her parents flew to the NIH Clinical Center at Bethesda, Maryland. There, over the course of twelve days, Anderson and his colleagues Michael Blaese and Kenneth Culver slowly extracted some of Ashanti?s blood cells. Safely outside the body, the cells had new, working copies of the ADA gene inserted into them by a hollowed-out virus. Finally, starting on the afternoon of September 14, Culver injected the cells back into Ashanti?s body.

The gene therapy had roughly the same goal as a bone-marrow transplant?to give Ashanti a supply of her own cells that could produce ADA. Unlike a bone-marrow transplant, gene therapy carries no risk of rejection. The cells Culver injected back into Ashanti?s bloodstream were her own, so her body recognized them as such.

The impact of the gene therapy on Ashanti was striking. Within six months, her T-cell count rose to normal levels. Over the next two years, her health continued to improve, allowing her to enroll in school, venture out of the house, and lead a fairly normal childhood.

Ashanti is not completely cured?she still takes a low dose of PEG-ADA. Normally the dose size would increase with the patient?s age, but her doses have remained fixed at her four-year-old level. It?s possible that she could be taken off the PEG-ADA therapy entirely, but her doctors don?t think it?s yet worth the risk. The fact that she?s alive today?let alone healthy and active?is due to her gene therapy, and also helps prove a crucial point: genes can be inserted into humans to cure genetic diseases.

From Healing to Enhancing

After Ashanti?s treatment, the field of gene therapy blossomed. Since 1990, hundreds of labs have begun experimenting with gene therapy as a technique to cure disease, and more than five hundred human trials involving over four thousand patients have been launched. Researchers have shown that it may be possible to use gene therapy to cure diabetes, sickle-cell anemia, several kinds of cancer, Huntington?s disease and even to open blocked arteries.

While the goal of gene therapy researchers is to cure disease, gene therapy could also be used to boost human athletic performance. In many cases, the same research that is focused on saving lives has also shown that it can enhance the abilities of animals, with the suggestion that it could enhance men and women as well.

Consider the use of gene therapy to combat anemia. Circulating through your veins are trillions of red blood cells. Pumped by your heart, they serve to deliver oxygen from the lungs to the rest of your tissues, and carry carbon dioxide from the tissues back out to the lungs and out of the body. Without enough red blood cells, you can?t function. Your muscles can?t get enough oxygen to produce force, and your brain can?t get enough oxygen to think clearly. Anemia is the name of the condition of insufficient red blood cells. Hundreds of thousands of people worldwide live with anemia, and with the lethargy and weakness that are its symptoms. In the United States, at least eighty-five thousand patients are severely anemic as a result of kidney failure. Another fifty thousand AIDS patients are anemic due to side effects of the HIV drug AZT.

In 1985, researchers at Amgen, a biotech company based in Thousand Oaks, California, looking for a way to treat anemia isolated the gene responsible for producing the growth hormone erythropoietin (EPO). Your kidneys produce EPO in response to low levels of oxygen in the blood. EPO in turn causes your body to produce more red blood cells. For a patient whose kidneys have failed, injections of Amgen?s synthetic EPO can take up some of the slack. The drug is a lifesaver, so popular that the worldwide market for it is as high as $5 billion per year, and therein lies the problem: the cost of therapy is prohibitive. Three injections of EPO a week is a standard treatment, and patients who need this kind of therapy end up paying $7,000 to $9,000 a year. In poor countries struggling even to pay for HIV drugs like AZT, the added burden of paying for EPO to offset the side effects just isn?t feasible.

What if there was another way? What if the body could be instructed to produce more EPO on its own, to make up for that lost to kidney failure or AZT? That?s the question University of Chicago professor Jeffrey Leiden asked himself in the mid-1990s. In 1997, Leiden and his colleagues performed the first animal study of EPO gene therapy, injecting lab monkeys and mice with a virus carrying an extra copy of the EPO gene. The virus penetrated a tiny proportion of the cells in the mice and monkeys and unloaded the gene copies in them. The cells began to produce extra EPO, causing the animals? bodies to create more red blood cells. In principle, this was no different from injecting extra copies of the ADA gene into Ashanti, except in this case the animals already had two working copies of the EPO gene. The one being inserted into some of their cells was a third copy; if the experiment worked, the animals? levels of EPO production would be boosted beyond the norm for their species.

That?s just what happened. After just a single injection, the animals began producing more EPO, and their red-blood-cell counts soared. The mice went from a hematocrit of 49 percent (meaning that 49 percent of their blood volume was red blood cells) to 81 percent. The monkeys went from 40 percent to 70 percent. At least two other biotech companies, Chiron and Ariad Gene Therapies, have produced similar results in baboons and monkeys, respectively.

The increase in red-blood-cell count is impressive, but the real advantage of gene therapy is in the long-lasting effects. Doctors can produce an increase in red-blood-cell production in patients with injections of EPO itself?but the EPO injections have to be repeated three times a week. EPO gene therapy, on the other hand, could be administered just every few months, or even just once for the patient?s entire lifetime.

The research bears this out. In Leiden?s original experiment, the mice each received just one shot, but showed higher red-blood-cell counts for a year. In the monkeys, the effects lasted for twelve weeks. The monkeys in the Ariad trial, which went through gene therapy more than four years ago, still show higher red-blood-cell counts today.

This is a key difference between drug therapy and gene therapy. Drugs sent into the body have an effect for a while, but eventually are broken up or passed out. Gene therapy, on the other hand, gives the body the ability to manufacture the needed protein or enzyme or other chemical itself. The new genes can last for a few weeks or can become a permanent part of the patient?s genome.

The duration of the effect depends on the kind of gene vector used and where it delivers its payload of DNA. Almost all of the DNA you carry is located on twenty-three pairs of chromosomes that are inside the nuclei of your cells. The nucleus forms a protective barrier that shields your chromosomes from damage. It also contains sophisticated DNA repair mechanisms that patch up most of the damage that does occur.

Insertional gene vectors penetrate all the way into the nucleus of the cell and splice the genes they carry into the chromosomes. From that point on, the new genes get all the benefits your other genes enjoy. The new genes are shielded from most of the damage that can happen inside your cells. If the cell divides, the new genes get copied to the daughter cells, just like the rest of your DNA. Insertional vectors make more or less permanent changes to your genome.

Noninsertional vectors, on the other hand, don?t make it into the nucleus of your cells. They don?t splice the new genes they carry into your chromosomes. Instead, they deliver their payload of DNA and leave it floating around inside your cells. The new DNA still gets read by the cell. It still instructs the cell to make new proteins. But it doesn?t get copied when the cell divides. Over time, it suffers from wear and tear, until eventually it breaks up, and its effects end.

The difference in durations among drugs, noninsertional vectors and insertional vectors gives us choices. We can choose to make a temporary change with a drug, which will wear off in a few hours or days; a semipermanent change with noninsertional gene therapy, whose effects will last for weeks or months depending on the genes and type of cell infected; or a permanent change by inserting new genes directly into your genome. Each of these three options is appropriate in certain situations. In the context of EPO, the idea of semipermanent or permanent change by means of gene therapy has definite advantages. It cuts down on the need for frequent injections, which means that the gene therapy approach can end up being much cheaper than the drug therapy approach.

Product Details

ISBN:
9780767918435
Subtitle:
Embracing the Promise of Biological Enhancement
Author:
Naam, Ramez
Publisher:
Broadway Books
Subject:
General
Subject:
Diseases - General
Subject:
Philosophy & Social Aspects
Subject:
Diseases
Subject:
Biotechnology
Subject:
Medical genetics
Subject:
Human reproductive technology
Subject:
General science
Copyright:
Publication Date:
20050308
Binding:
Hardback
Grade Level:
General/trade
Language:
English
Illustrations:
15 LINE DRAWINGS
Pages:
288
Dimensions:
9.3 x 6.4 x 1.1 in 1.15 lb

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Science and Mathematics » Biology » General
Science and Mathematics » Biology » Genetics

More Than Human: Embracing the Promise of Biological Enhancement Used Hardcover
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Product details 288 pages Broadway Books - English 9780767918435 Reviews:
"Publishers Weekly Review" by , "Imagine a person severely disabled by a stroke who, with electrodes implanted in his brain, can type on a computer just by thinking of the letters. Or a man, blind for 20 years, driving a car around a parking lot via a camera hard-wired into his brain. Plots for science fiction? No, it's already happened, according to future technologies expert Naam. In an excellent and comprehensive survey, Naam investigates a wide swath of cutting-edge techniques that in a few years may be as common as plastic surgery. Genetic therapy for weight control isn't that far off — it's already being done with animals. Countless people who are blind, deaf or paralyzed will acquire the abilities that most people take for granted through advances in computer technology and understanding how the nervous system functions. Naam says the armed services are already investing millions of dollars in this research; they envision super-pilots and super-soldiers who will be able to control their planes and tanks more quickly via thought. Some of the author's prognostications, with their Nietzschean overtones of people being 'more than human,' may frighten readers, but Naam is persuasive that many of these advances are going to happen no matter what, and that despite the potential for abuses, they offer hope for our well-being and the survival of the species." Agent, Ted Weinstein, Publishers Weekly (Copyright Reed Business Information, Inc.)
"Review" by , "An intriguing presentation by an unabashed advocate of the technological tricking and co-opting of mother nature."
"Review" by , "[R]eaders more interested in what's happening now in the biotechnology industry will get more from this work than those concerned with the bioethical implications for human identity."
"Review" by , "Ramez Naam provides a reliable and informed cook's tour of the world we might choose if we decide that we should fast-forward evolution. I disagree with virtually all his enthusiasms, but I think he has made his case cogently and well."
"Review" by , "More Than Human is excellent — passionate yet balanced, clearly written and rich with fascinating details. A wonderful overview of a topic that will dominate the twenty-first century."
"Review" by , "Sixty years ago, human beings gave digital computers the ability to modify their own coded instructions — sparking a revolution that has now given us the ability to modify our own coded instructions, promising revolutions even more extreme. Whether for, against, or undecided about genetic modification of human beings, you should read this book — a bold, compelling look at what lies ahead.'
"Review" by , "More Than Human is one of those rare books that is both a delightful read and an important statement. You'll relish the fascinating stories of physical and mental enhancement that Naam has assembled here, but you'll also come away with a new sense of wonder at the human drive for pushing at the boundaries of what it means to be human. No one interested in the future intersections of science, technology, and medicine can afford to miss this book."
"Review" by , "Ramez Naam's look at the coming of human enhancement is a major contribution; he shows convincingly that the conceptual wall between therapy and enhancement is fast crumbling."
"Review" by , "More Than Human is a terrific survey....Naam doesn't shy away from technical detail, but his enthusiasm keeps the science from becoming intimidating."
"Synopsis" by , Distilling the most radical accomplishments being made in labs worldwide, including gene therapy, genetic engineering, stem cell research, life extension, brain-computer interfaces, and cloning, More Than Human offers an exciting tour of the impact biotechnology can have on humankind.
"Synopsis" by ,
  • A man, blind for twenty years, can see when he puts on a pair of glasses connected to electrodes in his brain.
  • Gene therapy allows a young woman born with "bubble boy" disease to live normally among her peers.
  • Life-extension techniques promise to increase human life span by forty years or more.

It sounds like the stuff of science fiction, but these are true phenomena that have recently become hot topics in mainstream media. But while technology is enhancing the lives of many, it has also created a host of controversial capabilities, ranging from cloning to genetic engineering.

Distilling the most cutting-edge achievements being made in labs around the world, More Than Human offers an exciting tour of the way technology is impacting our lives. Throughout this remarkable trip, Ramez Naam shares an impassioned vision for the future, with revealing insight into the ethical dilemmas posed by twenty-first-century science. Encouraging us to celebrate rather than fear these innovations, his powerful book separates fact from myth with elegant lucidity, arguing that these controversial technologies have the power to transform the human race for the better.

More Than Human offers much-needed wisdom in the raging debates between technophobes and technophiles, and everyone else seeking to understand the marvelous possibilities that arise when mind meets machine.

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