DeCode Genetics: Genomics Studies In Iceland Precipitate Legal and Ethical Problems

The company deCode Genetics announced a number of discoveries this spring after analyzing thousands of human genomes, or complete DNA sequences, from the people of Iceland.  The company, bought in January 2015 by the Chinese company, WuXi Pharma Tech, is helping to usher in the Age of Genomics (click on the underlined word to view the link ), where precision medicine  attuned to patient genetic makeup will be practiced.  In other words, if your DNA is sequenced and you have a G here and a T over there, then your doctor can diagnose and hopefully treat you early for a given disease with a genetic component. Furthermore, if your DNA sequence and genetic risks are known, it’s easy to identify your relatives who may also be at risk for the same disease.  This is especially important where early diagnosis can affect quality of life or even survival, as in the case of hereditary breast cancer.  Other diseases reported on by deCode Genetics include dyslexia, schizophrenia, Alzheimer’s disease, and cardiovascular disease, among others (look here for publications). 
 

What is the DeCode Genetics study, what are the issues, and how do these issues concern you?  Read on to find out!

Figure 1. Drawing of DNA. Source: https://www.genome.gov/about-genomics

The Power of Ice(land)

The overall goals of deCode Genetics are to use population genomics to find common disease genes and then to use this information to help develop drugs for treatment of the diseases. To that end, DeCode sequenced the entire genomes of 2,636 Icelanders and also performed SNP analysis of 101,584 more.

In layman's terms, DNA sequencing of the entire genome,  down to almost the last A, T, G and C, is like watching a movie forwards and backwards in order to understand every frame.  Scientists at Decode “watched” the “movies” 20 times to make sure there were no errors in the DNA sequences they deciphered.  For all you DNA aficionados out there, both strands of all 46 chromosomes were sequenced.

SNP analysis, or single nucleotide polymorphism analysis, is like taking a snapshot of a movie at specified times in order to get a general idea of the “movie” or DNA sequence.  Scientists can even target analysis to specific “scenes” or genes.   

The people of Iceland were studied because the population is small, with about 270,000 people in 1997 at the beginning of the study (look here for population data).  Also, the people of Iceland have  a genealogy that is well studied with some family trees drawn back to about 900 A.D., when the country was founded.  Finally, the people of Iceland have national health care and medical records are readily available. All this data on so high a percentage of the population makes it easy to correlate mutations , or changes in the DNA sequence, with specific diseases. Moreover, if you have the family tree data, you can start with the data you know and you can infer what the genes and the disease risks of relatives are without actually having to sequence their DNA, in a process called imputation. 

Lawsuit Freezes the National Health Sector Database

The company DeCode was founded in 1996 and in 1998, the Icelandic Parliament passed the Health Sector Database Act, which allowed for the construction of three Icelandic databases for research. These included a genetic database, a genealogical one and one based on medical records.  By 2000, DeCode Genetics was licensed to construct the Health Sector Database (HSD) from the national health records. “Presumed consent “ was given for the genetic and genealogical databases, which meant it was assumed that everyone in Iceland would give consent.  However, there was an opt-out provision for people who did not want their medical records to enter the third database, the HSD. Many people had high hopes for the study bringing pharmaceutical money into Iceland. Eventually, though, 7% of the Icelanders opted out of the HSD due to privacy concerns. 

photo of worker with medical records, http://en.wikipedia.org/wiki/Medical_record

Subsequent laws eroded the HSD opt-out provision and in a 2001 lawsuit filed on behalf of Ragnhildur Guomundsdottir, a minor, by her mother asked the lower courts to uphold the girl’s right to opt-out of turning over the health records of her dead father to the HSD.  The case went through the courts until finally the Icelandic Supreme Court ruled in 2002 that the rights of the girl to opt-out of giving her dead father’s medical records to the HSD were protected. The ruling stated that genetic testing may affect people other than the one being tested and thus the girl’s right to privacy must be protected by protecting the privacy of her dead father’s medical records. You can read an analysis of the case here. This lawsuit effectively stopped construction of the HSD .

DeCode Genetics Frozen Out of Contacting Potential Cancer Patients

Fast forward to 2015.  If scientists at DeCode Genetics know either by direct evidence or by imputation that a person carries or has a high risk of carrying a mutation that can cause a preventable death, do they have an obligation to inform the person? Many would say yes, but the initial DeCode Genetics studies were begun with the promise that participants’ identity would never be revealed and the participants would never be contacted. This creates a dilemma where the company must chose between acting with moral conscience and contacting affected people or following medical ethics and not contacting them.

For example, scientists at DeCode have said that it would be possible to identify up to about 2,000 individuals who have inherited BRCA2, which greatly increases risk of cancer to the women and men who inherit it.  Early warning would allow affected women the opportunity to chose between careful monitoring for development of cancers and prophylactic removal of their breasts and/or ovaries in order to decrease the chance of getting and dying from cancer.  You can read more here to learn about DeCode's dilemma and here to learn about choices for women and men if they have inherited either BRCA1 or 2.  You can also read here about Angelina Jolie’s recent decision to undergo prophylactic  double mastectomy due to having inherited BRCA1, which is another inherited breast cancer mutation. The Icelandic Ministry of Welfare has convened a special committee to determine what to do in the case of deCode having important medical information that they cannot ethically reveal.  

What do you think deCode should do? Should they contact those people with genetic diseases for which there is a treatment or cure even though it is against medical ethics? Or, should they wait until the law is changed and then contact the affected people?  Or, should they allow residents of Iceland to opt-in if they wish to learn of diseases which may affect them?  

A Family Tree from http://ghr.nlm.nih.gov/handbook/inheritance/runsinfamily

President Obama Rolls Out Precision Medicine Initiative

If you’re wondering if genomics research and precision medicine will ever come to the United States, the answer is yes.  In fact, it’s already here and patients with cancer often undergo genetic tests to determine which treatments will best improve their chances of survival with minimal side effects.  

In January of 2015, President Obama in his State of the Union address requested $215 million dollars for the Precision Medicine Initiative to collect genomic data from 1,000,000 Americans with the hope of nudging the field of personalized medicine along.  The budget includes $130 million to the National Institutes of Health to collect the data, $70 million to the National Cancer Institute to advance cancer genomic studies, $10 million to the Food and Drug administration to work on the databases, and $5 million to the Office of National Coordinator to work on privacy issues.  You can read more here and here. 

Population genomics and precision medicine are the future of medicine and you’ll be reading a lot more about them in the future.  Careful consideration of the ethical and legal issues must be made in the U.S. and elsewhere in order to avoid some of the common pitfalls.