More Than Human; Embracing the Promise of Biological Enhancement

Book by Naam Ramez

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...