Human Genome Project Director Warns Against Genetic Tampering, Discrimination
By RONDA WENDLER
Texas Medical Center News
In the blockbuster movie Gattaca, a genetics doctor asks a husband and wife planning to conceive a child what traits they desire to see in their offspring.
“Would you like a boy or girl? How about musical ability, superior intellect, physical strength?” the doctor asks.
The couple exchange nervous glances, then tell the doctor their wishes.
“No genetic diseases, please. The rest we’ll leave up to chance.”
The doctor cautions them sternly that they must “design” a child as near to perfect as possible.
“Your child will still be you … but he or she will be the best of you,” he says.In Gattaca, set well into the future, children are made-to-order in a Petri dish. Only the best genes from mother and father are selected to increase the chance of having a near-perfecr baby.
While this Hollywood script makes for great entertainment, it’s largely fiction. Still, some scenarios in the movie are plausible, said Francis Collins, M.D., Ph.D.
A physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the National Human Genome Research Institute at the National Institutes of Health, Collins addressed an enthusiastic crowd at the University of Houston Jan. 17 in the final lecture of the “Medical Ethics and the Holocaust” series. Launched in September 2007, the series featured experts from across the nation who described how medical practices in Nazi Germany continue to influence modern medical ethics today.
The goal, said Collins, was to re-examine lessons learned and avoid going down the same path again.
“With the rapid pace of genetic discovery, there’s something serious at stake here as we contemplate our future,” Collins said. “By identifying genes associated with diseases, we have not only the chance to heal, but also the opportunity to harm. New opportunities for trouble are arising every day.”
A Bright Light
Genetics plays a part in virtually all diseases and illnesses, except trauma cases, Collins said. Most common diseases, like diabetes, are partly based in genetics and partly due to our environment – the foods we eat, the amount we exercise, whether or not we smoke, and other lifestyle choices. Several genes are usually involved, and when combined with environmental factors, the disease is activated.
In some rarer diseases like cystic fibrosis and sickle-cell anemia, a mutation in a single gene leads to disease. But in most illnesses, not just one, but several genes are involved.Even infectious diseases like AIDS are affected by genes, Collins said. Factors encoded by our DNA play a role in what happens to us after exposure to the pathogen.
“What scientists have learned about genetic susceptibility to AIDS has provided invaluable information,” Collins said, “that can lead to vaccines and preventive medicines.”
“If you want to understand a disease,” he said, “genetics gives you the opportunity to shine a bright light into the darkness of our ignorance so we can provide better ways to prevent and treat.”
Deluge of Discovery
In April 2003, the human genome was completed – all 3.1 billion letters of the human DNA instruction book necessary to make a human were spelled out for all to see. It was then, Collins said, that we learned a very important lesson: Every human on Earth shares 99.9 percent the same DNA.
“After learning this,” Collins said, “we began focusing on that one-tenth of 1 percent where we’re different.”
He is heading an international project in which six countries are trying to sift through that .1 percent of DNA to flag which genetic variations are connected with which diseases. The results have been astounding and fast.
“We’re making connections left and right,” Collins said. “It’s a deluge of discovery.”
The first success story occurred in 2005 when scientists found a mutation in a gene that leads to age-related macular degeneration, a condition that can cause blindness.
Treatments are being tailored to lessen that gene’s harmful effect.
In the last couple of years, dozens of connections between genes anddiseases have been made.
“Each of these discoveries points you in the direction of understanding that particular disease at a precise molecular level,” Collins explained, “and in doing so offers you a chance to develop a treatment that might be much more effective than what’s on the market now.”
He called this progress “exhilarating.”
“Now we can move away from a one-size-fits-all approach to medicine,” he said, “and we can tailor patients’ treatments to match their genetic profile.”
If an individual has a mutated gene, it rarely means the person will get the disease associated with that mutation. Almost always it means the person has an increased risk of getting the disease, compared to someone without the mutation.
A doctor who knows his patients’ gene mutations can advise those patients how to minimize their risk of getting those diseases.
“If you know you’re on the fence, you’re going to be more careful so you don’t fall off the fence,” Collins explained. “You’re going to watch what you eat, exercise, and do what your doctor tells you to do, unless you’re terribly stubborn.”
Similarly, knowing a patient’s exact genetic profile will enable doctors to prescribe medicine specifically tailored to that patient’s situation, as opposed to prescribing a drug that works in most people, but never in all.
Individuals respond to drugs differently, Collins explained.
“People with the same illness who get the same drug will get different results,” Collins said.
“Many will get well, but some will have no response. A few will even experience toxic side effects and have severe reactions.”
Pharmacogenomics – the study of how people’s genetic variations affect how they respond to drugs – will benefit patients enormously in the future, Collins said.
“This is personalized medicine. It’ll be standard in a few years, but already we can see it appearing.”
Don’t be surprised, he said, when in a couple of years your doctor refuses to write a prescription until he’s first looked at your DNA.
“He wants to make sure he’s prescribing the right medicine at the right dose specifically for you,” Collins explained.
A top national priority is preventing and treating cancer. To further this goal, the NIH established the Cancer Genome Project. Scientists participating in the project will analyze 50 types of tumors – brain first, then ovarian and lung, then assorted others to follow.
Their goal, Collins said, is to identify systematically “all the things that are wrong in the cancer cells that make up those tumors, then design drugs to address those problems.”
“This is our best hope for identifying new kinds of treatments that likely will be more effective for treating cancer than chemotherapy, which simply kills cancer cells that are dividing and multiplying.”
The leukemia drug Gleevec is a stellar example. Gleevec was formulated after researchers noticed that chronic myeloid leukemia almost always occurs in people who have a mutation in a particular type of blood cell. The mutation caused certain chemicals in the body to hijack normal white cells and turn them into malignant white cells, which is what leukemia is.
Researchers fashioned Gleevec to block this cell-hijacking process.
In the drug’s initial trial, Gleevec was given to 32 people who had advanced leukemia and were expected to live only weeks. Thirty-one went into complete remission. To this day five years later, most remain in complete remission and are living normal lives.
“We hope this is a dramatic foreshadowing of what may be possible with other diseases,” Collins said. “This is what can happen when you have precise molecular information that allows you to design a drug to target a specific problem.”
Progress and Pitfalls
But with progress comes potential pitfalls.Could our newfound ability to tinker with genetics somehow parallel the medical practices of the Third Reich, where Nazi doctors performed genetic experiments in hope of creating a superior master race? Or closer to home, will the way we handle genetics today echo a movement that was prominent in the United States prior to World War II, known as the eugenics movement?
Eugenics is a social philosophy which advocates the improvement of human hereditary traits through various forms of intervention. Throughout history, eugenics has been regarded by its various advocates as a social responsibility, an altruistic stance of a society, meant to create healthier and more intelligent people and alleviate human suffering.
Historically, eugenics has been used as a justification for state-sponsored discrimination, forced sterilization of persons deemed genetically defective, killing of institutionalized people, and even genocide of races or gendercide of sexes perceived as inferior.
From its inception, eugenics was supported by prominent people, including science fiction writer H.G. Wells, British playwright George Bernard Shaw, philanthropist and cornflake cereal inventor William Keith Kellogg, and birth-control activist Margaret Sanger who founded an organization that later evolved into Planned Parenthood.
Harvard, Princeton, Yale and Columbia Universities all offered academic programs in eugenics, with funding provided by such prestigious sources as the Rockefeller Foundation, the Kellogg Foundation, and the Carnegie Institution of Washington. Three international eugenics conferences presented a global venue for eugenicists with meetings in 1912 in London, and in 1921 and 1932 in New York.
But eugenics’ scientific reputation started to tumble in the 1930s when eugenic rhetoric became incorporated into the racial policies of Nazi Germany.
The public and the scientific communities began associating eugenics with Nazi abuses such as racial hygiene, human experimentation, and the extermination of undesired population groups.
“But let us remember that eugenics existed in the United States and in other countries before the Nazis practiced it,” Collins said. “Our hands are not clean.”
Well-intentioned people who supported eugenics thought they were doing the right thing by improving society and lessening suffering, Collins said, but somewhere along the way morality became twisted and spun out of control.
“The question is, could this happen again?” he asked. “With the genetic and reproductive technologies available to us today, how can we prevent discrimination and value life equally?”
Some people worry that their test results may become known to others. Suppose they test positive for a genetic disease. Will they lose their health insurance or jobs? Currently, there is no federal-level protection ensuring genetic privacy. Collins says one-third of people who sign up to participate in NIH trials involving genetic testing drop out when researchers cannot assure them that their information will remain confidential.
“Does this strike you as just … is this a good example of fairness?” Collins asked. “Is a society that won’t pass a law protecting people against genetic discrimination actually a eugenic society saying ‘those people who test positive for genetic diseases aren’t acceptable … we’re not going to cover their health care … we’re not going to ensure they have fair access to employment.’”
More than 40 states have limited genetic discrimination legislation in place, including Texas, but Collins said it’s a “strange patchwork filled with holes that allow you to get around the legislation.”
“The only effective way to offer people the protection they need and deserve,” he said, “is at the federal level.”
A genetic privacy bill is currently before Congress, but it’s been shot down in two prior legislative sessions. Collins says it’s anybody’s guess whether this year’s bill will pass.
“Some employers don’t want their hands tied – they want to be able to divest themselves of employees who are going to get sick and drain the company of resources,” Collins explained. “Those types of companies hire lobbyists to defeat bills that protect genetic privacy.”
Collins said he’s been asked several times to testify in favor of proposed legislation designed to protect genetic privacy.
“A staffer calls and says ‘We want you to come, but can you also furnish some victims who can testify?’”
“What’s the message here?” Collins asked. “Is this country not willing to take action until there are victims?”
Accentuate the Positive,
Eliminate the Negative?
While the majority of Americans believe genetics should be used to prevent or cure disease, some worry that it may eventually force us to decide which lives are worth living – and which lives are not.
Take, for instance, Down syndrome. At least 80 percent of pregnant women who undergo amniocentesis and test positive for Down syndrome choose to abort. Yet today many people with Down syndrome live happy, productive lives. The average life span for a Down syndrome patient is 49 years, up from 25 years in the early 1980s.
“So who’s to say what is and what isn’t a worthwhile life?” Collins asked.
Others worry that genetics will be used for frivolous purposes, like enhancing personal traits that are not associated with disease, such as hair color or eye color. Specifically, their concern is with a technique known as pre-implantation genetic diagnosis, which is being used now to help couples bear children free of devastating genetic diseases.
Here’s how it works: Using the father’s sperm and mother’s eggs, several embryos are produced in a test tube. Each embryo then undergoes genetic testing, and the “best ones” – those free of hereditary diseases – are transferred back to the mother’s womb for implantation.
“You’ve got to wonder, what are the limits here?” Collins asked. “Today we don’t select the embryos with genetic diseases, but tomorrow we might avoid selecting the embryos that contain genes for obesity. In a few years when we discover genes for intelligence, we’ll likely start selecting embryos based on intellect. How about muscle strength, tallness or shortness, or anything that’s not a disease?” he asked. “Exactly where do we stop?”
Already pre-implantation genetic diagnosis is being used to select male and female babies.
In the United States the birth ratio is 105 boys born for every 100 girls. But in countries where boys are prized, that ratio is much higher in favor of boys. In China, it’s 120 boys to 100 girls, and in India it’s 117 boys to 100 girls.
“Since when is being a boy or girl a disease?” Collins asked. “This is clearly eugenics. We do it in this country, too, but we call it ‘family balancing.’”
Many questions regarding our use of genetic technology must be answered, and policies put in place. Until then, Collins says one thing is certain: “The most unethical thing we can do is stop genetic research for a few years until we figure out how to solve all the ethical problems. I don’t know how I could tell a dying patient who is fervently waiting and hoping for a breakthrough that we’ve stopped for awhile so we can sift through the ethical consequences.”
And despite our ability to re-direct our genetic destiny, Collins said, genetics will never be able to change human nature.
“We are still individuals uniquely gifted with a conscience, a sense of right and wrong, and a free will that allows us to choose how we want to use our knowledge,” Collins said. “All the science in the world is not going to trump that or make that an illusion. We should celebrate that we are not the victims of biology any more than we let ourselves be. We have a chance to use our free will to make the right decisions.”
MAPPING THE FUTURE—Francis Collins, M.D., Ph.D., head of the National Human Genome Research Institute at the National Institutes of Health, spoke in Houston Jan. 17 about the Human Genome Project’s implications for the future. The project was completed in 2003, and identified all genes in human DNA. (Photo by Steve Ueckert)