Who We Are

I fell down a few years ago and scraped some skin off my face. It eventually healed, but for awhile I had an expanse of angry red flesh spread across part of my cheek and forehead. Whenever I entered a restaurant, I was struck by how quickly heads turned to view me, and then, of course, looked away as I returned their stare. Funny, younger children kept staring when I looked back. We are fascinated with differences, perhaps innately.

Airports are amazing. Occasionally I amuse myself by examining the many faces coming toward me as I walk down the terminal toward my gate. Perhaps it’s a quest for the familiar face, especially in Houston. But I have also played this game in LaGuardia or Schiphol. Each time the astonishing array of different faces shows how much variation there is between us—genetically.

That level of variety is not obvious when I gaze at other animals. Gazelles all look alike to me, so do penguins. I once heard on the NBC Today show that the only way scientists can tell the difference between male and female king penguins is by dissection. To paraphrase Tom Brokaw, presumably the penguins have a more subtle way of telling each other apart. Maybe they have different smells or eyebrow hairs. Who knows?

This fascination with human differences partly explains why scientists are analyzing human genetic variation. Technology is now catching up with curiosity, and major discoveries about people’s genes are announced almost every day. Yesterday’s buzzword was the human genome, and is now being replaced by the personal genome. The human genome—a DNA instruction book for building and running a human machine—turns out to be really, really variable from person to person. The variation in personal genomes is so unexpectedly large and interesting that Science, the Time magazine of the scientific world, declared human genetic variation the most important breakthrough of the year 2007.

A key observation came from Craig Venter. Venter made his name in 2001 by sequencing the human genome. He then teamed up with a private firm to begin sequencing a personal genome. The badly held secret was that much of the DNA for his company’s version of the genome came from Venter’s blood and sperm. In 2007, his company made it official: they published the personal genome of Craig Venter in the Public Library of Science (PLoS) Biology: “The Diploid Genome Sequence of an Individual Human”.

I believe the PLoS paper is a landmark paper. For the first time in history, scientists were able to compare the sequence of DNA from Venter’s dad to that from his mom, although the exact assignment of mom versus dad awaits information from their DNA. This new information shows much more genetic variation between parental DNAs than previously realized. The DNA of Venter’s mom is about 99.5% identical to that of his dad. The differences (0.5% is a lot) included many large insertions and deletions, not just changing one nucleotide, the bulding block of DNA, for another here and there. Which differences make the man is still a huge mystery.

Another first is that Venter put his name on his own genome. He chose to forego the usual privacy concerns so that the predictions of this DNA handbook could be compared against his person. This publicity promotes Venter’s work. The possibility that people will elect to reveal their genetic information for public good or personal gain was voiced by Rice President David Leebron at the Fifth De Lange Conference in 2005. This license raises several troubling issues. What about selecting a spouse, qualifying for a job, or getting on a peewee football team—who has the right stuff? You cannot ask, but what if someone tells you?

Or can you ask? A NASA official once told me that the organization was considering introducing genetic screens for astronauts to see who is better able to repair their DNA. Apparently space radiation is so strong that most humans may not survive an extended space flight to Mars. The ability to repair DNA damage protects against radiation damage and even cancer, and some people are likely to have a better innate ability to fix their DNA. Billy, a childhood friend of mine, had a mom who could have been a great Mars astronaut; she was a chain smoker her whole adult life and never developed cancer. I haven’t heard of such a screening program getting started, perhaps because a balance between concerns for astronaut survival and individual privacy is difficult to achieve.

There are other major concerns about this new information entering the public arena. Any property which distinguishes one group of people from another is a potential wedge for us versus them thinking, such as profiling that leads to prejudice. Historically, the most divisive of this thought have been attempts to link human capabilities, such as IQ, to a certain ethnic origin or race. But mainstream society has turned a hard corner against such leanings, which are definitely not supported by data. James Watson, the most well-known genome scientist, was recently shunned and expelled from the scientific community for suggesting an IQ-race link. Another concern is how far DNA information can be used in law enforcement. A recent Wired magazine article points out that police are very reluctant to use a DNA-based race identification test called DNAWitness to narrow the field of suspects in cases, even though this technology has been helpful to them on several occasions. One prosecutor said that he dislikes anything that implies we don’t all bleed the same blood.

The Venter genome is the opening note in this nearly endless symphony surrounding personal genomes. A vigorous competition, hosted by the X PRIZE Foundation, is now underway to reduce the cost of a personal genome, so that many can be analyzed and the variations in the DNA correlated with various and sundry human traits. Then, with your personal genome and this database, you will know where you come from and what kind of medicine fits you best. Three companies—23 and me, Decodeme, Navigenics—are jumping the gun and offering personal genome information analysis as we speak. These recent startups are certainly too premature; knowledge of the connection between DNA differences and personal health issues is much too limited right now. In spite of the novelty, I wouldn’t waste my money on their service.

Despite these limitations in personal genome interpretation, I suspect that, someday, most people could and will have their genomes scanned. There will be clues about family origins and the propensity for specific diseases or certain behaviors. You may even join an online community of people with similar genetic features. A benefit to you and the pharmaceutical industry will be predicting your reaction to prescription drugs. New drugs are often pulled during the testing phase because a fraction of treated people receive no benefit, or worse, get sick from the medicine. With a database of genome-reaction information, more drugs may survive the gauntlet of testing and be available for purchase, with genetic restrictions for their use.

But, assuming the sophistication of this personal genome-based database grows and grows, can there be a limit to our knowledge? Certainly our upbringing and lifestyle help determine who we are, although identical twins raised separately show unexpected similarities in personalities, including shared political affiliation, car preferences, etc.

But are such traits as laughter types and other readouts of brain activity strictly matched between “identical” twins? Maybe not. Rusty Gage at the Salk Institute found that brain cells, when first formed, will mutate and change their DNA in random fashion. Such large-scale mutations do not occur in cells for other developing tissues of the body. Then, some brain cells survive and others are culled from the developing gray matter.

I remember listening to Gage present his results and the hairs went up on the back of my neck, something that doesn’t happen to me very often. His data suggest that the brain is a complex mosaic of genetically different cells, formed by the two basic processes of evolution—generation of diversity followed by selection—all acting in one person. Our personal genome will be read from the DNA of readily accessible cells, typically from a sample of blood. Thus, the most central part of humanness, the thinking of our brain, may not be largely predictable from a genome scan. I don’t know how I feel about all this complexity. I will miss the word “simple” because it relaxes me. “Complex” makes me tense, like maybe I can’t understand. But then, nonetheless, I can keep on scanning faces in airports, wondering and wondering if I’ll ever see my twin.