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Genes, Therapy & Identity | When We Cease Being Us?

Genes, Therapy & Identity | When We Cease Being Us?

Artist © Piet Zwaanswijk

What do these statements have in common: “Know thyself,” “The Genetic Code,” and “You are what you eat”?

They all point to the human quest for identity, the search for what makes us unique. And while the science of genetics has allowed us to know ourselves better, it also opens the door to disturbing questions, including: “Is our DNA destiny?” “Should we clone people?” “Does gene therapy take away our identity?” “Is GMO food so unnatural that it can harm us?”

On July 17, researchers from the University of Massachusetts announced in Nature that they had found a way to “silence” the extra chromosome that causes Down syndrome, a genetic disease that affects 1 in every 300 newborn babies. “The last decade has seen great advances in efforts to correct single-gene disorders,” said biologist Jeanne Lawrence, who led the study. “By contrast, genetic correction of hundreds of genes across an entire extra chromosome has remained outside the realm of possibility.”

In depth |’Silencing the Down Syndrome chromosome’ 
Jeanne Lawrence and her team found that by using the same molecule that keeps females from over-expression of their extra “X” chromosome, they could shut down the expression of genes on the extra 21st chromosome carried by people with Down Syndrome. Gene therapy or prevention of the disorder would depend on the ability to identify and shut down specific genetic pathways and mechanisms started by the presence of the extra chromosome. The molecule used for shutting down chromosomes, an RNA molecule called XIST, is effective at shutting down similar pathways on the human X chromosome, which then prevents genetic disorders in women (who carry two X chromosomes). The researchers first found a way to insert the X chromosome’s XIST molecule into one copy of chromosome 21. XIST works not by coding for a protein itself (a normal part of gene expression), but instead by regulating the actions of other genes. By inserting XIST in induced adult stem cells of patients with Down Syndrome, they were able to see the effects of shutting down the chromosome in cells. XIST operates by modifying chromosome structure so that its DNA can’t be expressed anymore, rendering most of the genes.

Indeed, gene therapy has improved from a very shaky start 20 years ago to provide some effective treatments for a number of disorders, most of them rare and caused by one gene. Now, if we can shut down the activity of all genes on a chromosome, the power of manipulating genes becomes a lot greater.

Nick Bostrom, director of the Future of Humanity Institute at Oxford University, points to a possible collision between the rise of genomic-based medicine and the sense of “self.” In a report for the UK’s Government Office for Science, Bostrom points out that we look at our DNA as a form of our “true self,” which “embodies some form of essentially genetic identity,” he wrote. While today, gene therapy and alteration of gene expression (silencing bad genes, and encouraging good ones) are used to treat disease, there are also efforts to apply these techniques to enhancements, improving memory, slowing aging, increasing athletic strength and running speed or endurance. These developments may take another 15 years, but once they happen, they could dramatically change what it is to be human.

“You can engineer a prairie vole to become monogamous when it’s naturally polygamous. It’s just a single gene. Might be more complicated in humans, but perhaps not that much,” Bostrom told his TED audience recently. This underscores another issue with genes as identity; the deliberate passage of modified genes through generations. This can happen by modifying germ cells (eggs and sperm, for us), or by cloning.

Cloning had a spectacular entrance in 2000, with the announcement by Korean researchers that they had indeed created a new human being purely by cloning.

Not to be outdone, a group in the Bahamas also announced a cloned human. The Caribbean group, the Raelians, who believe we were created by aliens from outer space, never produced any cloning evidence, while the Koreans’ evidence, published in Science, turned out to be fraudulent. But the concern over cloning and germline manipulation continues. Should we be able to make humans purely for laboratory use (similar to a “parts car” used by auto enthusiasts)? How much should we change identity and pass it on to future generations?

In depth | What is cloning?
There are actually two types of cloning. One, which gets all the media attention, is the reproduction of an exact copy of an organism. Identical twins are clones, though they obviously aren’t made in a laboratory. Dolly the sheep was a clone of his type. The other type of cloning goes on in laboratories all the time, and involves making copies of a part of DNA (usually, but not always, a gene). This piece of DNA is then copied, or cloned, multiple times to make studying of it easier.

Tweaking our behavior

An extension of changing genes is behavioral genetics. In this growing field, scientists are looking not only at ways to treat psychiatric and developmental disorders of the brain (including Down syndrome, but not limited to that), but also at ways to enhance brain function (including memory and intelligence). With more than 1,000 genes estimated to in some way control behavior, this is a tall order.

Behavioral genetics didn’t get off to a good start. Sir Francis Galton was the first scientist to study both heredity (“genetics” as a term didn’t arise until just before his death in 1909) and behavior, with studies on the behavior of twins. In 1907, he also wrote Inquiry into Human Faculty and its Development, which detailed what he believed were inherited criminal traits: deficient conscience, vicious instincts, weak self-control, and an unwillingness to hold a steady job. And things got worse, much worse. In the United States, a Eugenics Record Office put Galton’s ideas into mainstream science and government policy, resulting in tens of thousands of forced sterilizations tied to “hereditary fitness.” Nazi Germany further honed these ideas into Hitler’s proclamation of the “master race,” and justified the atrocities of the Holocaust.

Today’s scientists are hardly practitioners of eugenics, but some research studies have sparked concern. Colleen Berryessa and Mildred Cho of the Stanford University Center for Biomedical Ethics, warned in a February Annual Reviews in Genomics and Human Genetics that even with tools like whole-genome sequencing, non-invasive genetic testing and the ability to detect behavioral biomarkers, “behavioral genetics is also subject to the naturalistic fallacy, that if it is natural, it must be good.” They point to scientists who assumed that if homosexuality or mental illness has a genetic connection, the stigma of those conditions can be removed. There also still exists the “fallacy of heritability—if a trait if heritable, it is unalterable by environmental changes,” Berryessa and Cho say.

Meanwhile, a number of research groups are searching the genome for clues behind a range of behavioral disorders, using genes from children diagnosed with such disabilities. About 2% of all children have some intellectual disability. Han Brunner, a medical geneticist at the Radboud University Nijmegen Medical Centre in the Netherlands, leads one of the projects to find genetic links to these disorders. So far, Bruner has sequenced 100 protein-producing genes (known as “exomes), and found new mutations that could cause the disorders in about 40% of the children whose genes he sequenced. But many of these mutations may not be helpful in diagnosis—every healthy human genome has about 100 gene-altering mutations.

Behavioral genetics may have come a long way from finding ways to boost IQ (or sterilize those who have low IQ scores), but a new study by a Chinese group using data from programs for precocious youth in the US is facing skepticism. BGI (formerly the Beijing Genomics Institute) researchers are sequencing the genomes of 1,600 youth, to search for clues behind their genius. They are traveling over a road that’s littered with failure—no previous intelligence studies have delineated a clear genetic connection.

One reason for that failure might lie in the way we perceive the brain. Neuroscientist-turned author Robert Burton thinks that one reason for these studies’ failures lies in what we consider the brain, versus the mind. Recently, he told Salon:

“The mind exists in two separate dimensions – as the subjective experience of what goes on inside our heads, and as abstract concept. Neither can be objectively assessed. We can study brain function and ultimately arrive at a good working model of how the brain works. However, there is no scientific method to address subjective experience. The Holy Grail of neuroscience would be to understand how the brain converts biological activities into subjective consciousness. Presently we have no clues, not even reasonable suspicions.” Given this framework, the mind is unlikely to connect to any given gene (or group of genes).

What—or who—am I eating?

What we eat means a great deal to us. In America and Europe, people want their food to be safe; this is one consistent argument made against GMOs (genetically modified food). But safety of food did not suddenly start with GMOs, and in fact, genetically engineered crops were introduced as an alternative to harmful pesticides and fertilizers, which do remain on crops after after they’re sold in a market.

Could the idea of genetically modified organisms—those carrying a “foreign” strip of DNA—be triggering an identity crisis, much like gene therapy or altering behavioral genes? One criticism of GMO food is that people can ingest “foreign” DNA; if this were true (and many scientists say it isn’t), the same ingestion would occur with non-GMO preparations. But these new types of food introduce something that isn’t seen as “natural;” hence the epithet, “Frankenfood.”

Since the practice of genetically modified crops started in 1996, the amount of land under GM cultivation has increased from 1.7 million to 170 million hectares (70 million of those in the US). About 17.3 million farmers planted GM crops last year. According to the International Service for the Acquisition of Agri-Biotech Applications (ISAAA), the economic benefits of such crops totaled US$10.1 billion for developing countries, and US$9.6 billion for the developed world.

In depth |’ What is GMO?’ 
GMO, or genetically modified organisms, are living cells that have genetic material from another source inserted into their genomes. Using modern genetic engineering techniques have allowed scientists to take DNA from a plant, animal or microorganism that may provide a beneficial property (like resistance to pests, or growth booster), and insert that DNA (and benefit) into a host animal. The practice is similar to traditional breeding techniques that required the selection over generations of a desired trait. Only with GMO’s, the gene itself is altered.
But opposition from non-government agencies and members of European parliaments have limited European approval of just two GM technologies; the use of a gene from a bacteria (Bacillus thuringiensis) that resists insects in corn, and a potato that has been altered for a different starch composition. While there are some concerns about gene therapy, none equal the weight of opposition to genetically modified food.

Why?

Sir Brian Heap, president of the European Academics Science Advisory Council in Halle, Germany, says there are a number of factors:
“First, there was a lack of need (for GM food) in the EU when it was first produced in ‘80s and ‘90s because there were ‘milk lakes’ and ‘grain mountains’. This generated many negative views which persist,” he said, warning that population growth is quickly eating into those lakes and mountains. In addition, NGOs and citizens of Europe “reacted against the tactics of multinationals who pushed the technology when it was perceived to be unwanted.” And finally, Heap offers a kicker: “Residual and deeply felt ‘anti-genetics’ views of the European Green movement reflecting fear of what happened in the Third Reich.” Eugenics redux.

What’s the answer?

While there are legitimate scientific and social concerns about the use of genetics to treat disease—they often don’t work, can cause more harm, and play into the hands of modern-day eugenicists—there is a bright light, and it lies in DNA. Just not the DNA in genes.

It turns out that DNA isn’t destiny after all. The relatively new science of epigenetics, which studies the so-called “junk” DNA that comprises about 98 percent of our genomes, makes sure that environmental factors are just as big a part of our destiny as any gene that can produce a protein. As Dana Dolinoy, a researcher at the University of Michigan School of Public Health put it; instead of showing our genes shape our lives, “we see how our lives shape our genes.”

In fact, even genetically modified food isn’t based on inserting a gene anymore. The second-generation of GMO includes techniques that include transferring a gene to a plant of the same species (instead of from a bacteria or totally different plant), inserting a reorganized portion of a gene from the same species that can produce a different type of plant, and the use of non-coding, “epigenetic” stretches of regulatory DNA or RNA that can influence behavior of genes, without creating a new gene itself. According to EASAC’s Heap, the European Union isn’t sure how to classify these new techniques, since they aren’t really genetic modifications.

We are, then, our environment. And our environment, whether of mind, air, food, water or family, is us.

This article was originally published in the tablet issue Plastic Fantastic | The Cardboard Issue

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