Famous folk have been writing about their genome sequences for a few years now. But when I received two such reports at once last week – about genetics researcher Ron Crystal, MD, and a hypothetical (I think) story about President Obama, I knew it was time to take action.
Or, in my case, inaction.
After writing ten editions of a human genetics textbook and lots of articles, you’d think I’d be first in line to get my genome sequenced. But I prefer ignorance.
The quest to know ourselves by our DNA sequences began in the late 1980s, with the conception of the human genome project, and reached a milestone with the actual genome sequencing.
Revisiting the Genome Race
I still have my dog-eared copies of the journals unveiling the first draft of “the” human genome, from February 2001. The Science report hailed from the Celera Genomics/Craig Venter camp, with 5 individuals contributing to that composite genome, including CV himself, who has since gone on to creating life. The Nature report represented the International Human Genome Sequencing Consortium, which used genome pieces from several de-identified individuals.
On June 26, 2000, Francis Collins, MD, PhD and Craig Venter, PhD, flanked President Clinton in the White House rose garden to announce the great sequencing, because that was the only available date on the calendar. Both groups had made nice at the end of the race. Celera actually crossed the finish line first, as Dr. Venter told me that February off the record, lest the looming new edition of my textbook be obsolete. Today the race seems irrelevant.
The First Two: Craig Venter and James Watson
By 2007, individuals began to have their genomes sequenced, and speak and write about it. Dr. Venter was first, his genome presented in PLoS Biology. He pondered the implications at the American Society of Human Genetics annual meeting a year later.
Dr. Venter learned from his genome sequence that he has blue eyes and a tendency toward antisocial behavior, substance abuse, and novelty seeking. He found out he’s a fast caffeine metabolizer. “I can have two double lattes and wash it down with a Red Bull and not be affected by it,” he snarkily told the crowd. He also learned of elevated risk for Alzheimer disease and cardiovascular disease.
Next came James Watson, PhD, of double helix fame and first head of the human genome project. He discussed his genome at the 12th International Congress of Human Genetics in Montreal in October 2011, where Kevin Davies, PhD, author of “The $1,000 Genome” introduced him. Dr. Davies has subjected himself to all manner of genome probings too. Here’s the printable part of what Dr. Watson said:
Why did he do it? “Why not? I had no objection, with the exception of not wanting to know ApoE4. My grandmother had Alzheimer’s.” (Watson’s published genome sequence omits that risk gene, but people imputed it from the surrounding sequence.)
What did he learn that was useful? “Finding that I am a slow metabolizer of antipsychotics and beta blockers.” His son nearly died from an antipsychotic. “So I now know that if I go psychotic, I can’t take those drugs.” And he learned why beta blockers for an irregular heartbeat knocked him out. He switched drugs.
What information wasn’t helpful? “They told me I was a carrier for BRCA1. I thought I would have to phone my nieces because their mother had breast cancer. But I asked Mary-Claire King, who discovered the gene, and she said no, I had a harmless variant. So I’m glad I didn’t call my nieces because then they would have paid that disgraceful sum of money to Myriad Genetics.”
Dr. Watson ended with a situation he knows well. “I’d like to see children who have mental illness sequenced with their parents. Finding a mutation would make parents see that it was genetic injustice. Knowing that won’t make their child healthy, but they won’t have the double whammy of thinking they did something wrong.”
Dr. Venter wryly summed up the great personal value of he and Dr. Watson knowing their sequences. “You probably wouldn’t suspect this based on our appearances, but we are both bald, white scientists.”
Genome Sequencing in Sickness and in Health
Genome and exome sequencing are extremely valuable in diagnosing people whose symptoms don’t match known disorders. “Every time someone goes into a children’s hospital with a serious disease, it would be immoral NOT to sequence him,” Dr. Watson said. The first and most famous case is that of young Nicholas Volker and his intestinal condition; I’ve followed that of 4-year-old Gavin Stevens’s blindness gene. The cases of exome sequencing solving medical mysteries are mounting fast.
Steve Jobs and Christopher Hitchens had their cancer genomes sequenced, pancreatic and esophageal, respectively, and the information guided drug choices. Henry Louis Gates Jr. had his done to trace his ancestry. Glenn Close reportedly did it to better understand mental illness in her family, and I can’t guess why Ozzy Osbourne did it.
Ron Crystal, chairman of genetic medicine at Weill Cornell Medical College, had his genome sequenced to provide a control in a project to sequence the genomes of the people of Qatar. He discovered a mutation that explained his heavy bleeding following an injury from rappelling off a frozen waterfall a few years ago. He also discovered Viking roots, a recessive disease of children, and confirmed his baldness. But he voiced fears: his family learning things they didn’t want to know, even someone using his DNA sequence to frame him for a crime or to clone him.
Dr. Crystal isn’t the only one to cite potential repercussions of knowing one’s genome sequence. Said Seong-Jin Kim, the first Korean to have his genome sequenced, and that of his wife and two daughters. “Genetic disease in Korea is thought to disgrace families, and so it’s difficult to convince families with diseases to be sequenced.” A bad result could be regarded as a curse. But he was interested in using sequencing to better understand gastric cancer, which is the most common form in Asia. “Did it change attitudes? After we released our sequence, the number of sequencing companies increased.”
Why I Don’t Want to Know
I don’t want to know my genome sequence because of a fear that someone will clone me, but because the state of the science provides both too much and too little information.
On the TMI front, a genome sequence is a mega incidentaloma, an avalanche of information I don’t want. A panel discussion on the value of genome/exome sequencing at the international congress last year was telling.
Opinions ranged from moderator Han G. Brunner, of University Hospital St. Radboud in Nijmegen, the Netherlands, who asserted that “genome sequencing will yield an excess of information that is useless, uninterpretable, and possibly damaging to the patient” to Radoje Drmanac, co-founder and CSO of Complete Genomics, who claimed “We should have our genomes sequenced as early as possible. In my mind, this is not a question.” (Disclosure: Just before the panel discussion, I ate mozzarella sticks from Complete Genomics when I wandered into a cocktail party whilst hunting and gathering. I wonder if they got my DNA from the napkin.)
At the top of the list of diseases I don’t want to know about are those of the brain, Woody Allen’s second favorite organ. If I can’t prevent or delay them, why spend years worrying?
On the too little information front, we need to know more than a string of DNA letters or a list of gene variants. We need to know how our genes interact. It’s like reading a novel and considering each word in a vacuum, compared to understanding the unfolding story.
Learning our genetic story will require deciphering all possible gene interactions. Until then, I might learn about a disease-causing mutation, but not another that counters it, and then have to live with the knowledge. Computers and researchers will need to dissect and compare many thousands of sequenced human genomes to deduce the gene interactions.
All the needed analysis is costly. Bruce Korf, MD, PhD, director of the Heflin Center for Human Genetics at the University of Alabama at Birmingham has said, “We are close to having a $1,000 genome, but this may be accompanied by a $1 million interpretation.” And when Stephen Quake, a Stanford University engineer and co-inventor of a DNA sequencing device, laid his genetic self bare in the pages of The Lancet in 2010, interpretation required 32 physicians.
Like the others mentioned, Dr. Quake found the drug information the most valuable. He leads a very healthy lifestyle, but has gene variants that raise risk of cardiovascular disease. His genome revealed that a statin drug could save his life, the bloodthinner Plavix won’t work, nor would the diabetes drug metformin. But could carefully-chosen panels of single-gene pharmacogenetic tests provide the same information, based on the age-old tool of genetic counselors, asking good questions to build a useful family history?
Next week I’ll be at the American Society of Human Genetics annual meeting, attending workshops on exome/genome sequencing and hunting for more mozzarella sticks. And I’ll see if anyone can convince me to have my genome done.
Perhaps I’ll do it, eventually, as part of the Personal Genomes Project, for the greater good, but elect not to know the results. After all, I already know the obvious, like Craig Venter knows he’s bald and has blue eyes.
An osteoarthritis mutation manifested itself as an inability to play an F chord at age 33. A p53 mutation and then another that bloomed in response to years of orthodontia X-rays gave me thyroid cancer a few years after I gave up the guitar. And I don’t need a genetic test to know I didn’t inherit my father and grandfather’s psychotic depression.
Ron Crystal, even though he’s among the sequenced, has the right idea: don’t smoke, exercise, eat a healthy diet, and don’t worry about DNA sequences.
That’s good enough for me – at least for now.
This was first published on November 1st on the PLOS blog. Click here to read the original article.
Ricki Lewis is the author of "The Forever Fix: Gene Therapy and the Boy Who Saved It," St. Martin's Press, March 2012. To read more blogs from the author, please visit her site at http://www.rickilewis.com.
The Alden March Bioethics Institute offers a Master of Science in Bioethics, a Doctorate of Professional Studies in Bioethics, and Graduate Certificates in Clinical Ethics and Clinical Ethics Consultation. For more information on AMBI's online graduate programs, please visit our website.
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BIOETHICS TODAY is the blog of the Alden March Bioethics Institute, presenting topical and timely commentary on issues, trends, and breaking news in the broad arena of bioethics. BIOETHICS TODAY presents interviews, opinion pieces, and ongoing articles on health care policy, end-of-life decision making, emerging issues in genetics and genomics, procreative liberty and reproductive health, ethics in clinical trials, medicine and the media, distributive justice and health care delivery in developing nations, and the intersection of environmental conservation and bioethics.