Personal Genomics: Who owns your genome?

What is personal genomics? What is it used for? What sort of ethical issues surround this technology in society?

EDIT: At 7:54 I describe Huntington's Disease as recessive but it is dominant

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Children of the 80s will recall vividly the opening sequence of the sci-fi movie, Gattaca, where a genetic test at birth determines that the protagonist of the movie, Vincent, a genetic invalid. He has a high likelihood of various diseases including a 99% probability of a heart disease and death by 32 years. This prognostication has a huge impact on his future, limiting insurance, childcare, education and most choices in life. The impact of being a genetic invalid, is so dire that his parents decide to screen the embryos for his sibling, Anton, prior to implantation so that he is free of any dispositions to any genetic disadvantages ranging from baldness, to myopia and obesity on the grounds that “they want the best child they can possibly have”. The movie goes on to follow Vincent as he attempts to overcome his dire genetic lot in life and become a space traveller by buying someone else’s genetic identity.  

Whilst Gattaca and the sort of future it describes sits in the realms of science fiction, some worry that current genetic technology may lead us in a similar direction.  I’m your host Dr. Rachael Brown and today in the p-value we will explore the reality of contemporary personal genomics. What sorts of things can and can’t we do with personal genomics technology? What can we expect in the future? And what sort of ethical conundrums does it raise?

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Personal Genomics is an umbrella term which covers a range of technologies for sequencing, analysing and interpreting the genomes of individuals. Most of you listening to this podcast will probably have had a genetic test even if you don’t realise it. In Australia, newborn babies are routinely tested for cystic fibrosis, phenylketonuria (or PKU) and a variety of other serious diseases that may not be obvious at birth via the government funded Guthrie or heal prick test. You also likely know people who have had other genetic screening or testing such as testing for a disposition to Breast Cancer, prenatal genetic testing like the NIPs test, or an Ancestry.com or 23andMe ancestry analysis. 

All these sorts of personal genomics technologies involve taking a small sample of DNA, typically in blood or saliva from an individual. The DNA within the cells in that sample is extracted and amplified through various techniques. All or parts of the code of amino acids which make up the individual’s genes are then sequenced. Once the genetic information has been obtained in this way, various analysis techniques can then be applied to it to work out what that genetic information can tell us about the individual. In some cases, there is a particular target gene or genes which is being looked for, as in the case of testing for the absence or presence of particular disease-related genes such as in the testing for cystic fibrosis via the Guthrie or heel prick test. In other cases, such as in the sort of direct-to-consumer testing done by companies like 23andMe and AncestryDNA, larger strings of DNA are compared with large databases to make claims about ancestry, relatedness and disposition to certain traits. 

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Personal Genomic Tests are done for many purposes. 

In the case of direct-to-consumer testing such as 23andMe or Ancestral DNA the interest is typically in ancestry or curiosity. Many of you will know, for example, people contacted by long lost relatives found via direct-to-consumer testing. Or those that swear their family came to Australia with the first fleet on the grounds of such a test. 

Genomic analysis done in a more medical context through a GP or specialist is typically focused on improving health and wellbeing and takes several forms. There are tests for the presence or absence of specific health conditions. These include testing for simple genetic disorders like huntington’s disease and Tay-sachs disease where the presence of particular genes determines whether or not you have the disorder. There is also testing for the presence of genes that dispose us to more complex traits such as type-2 diabetes, some cancers and heart attack where the genes inform us of a risk but not with certainty of whether or not you will get the disease. There is also prenatal and pre-implantation screening for health conditions in embryos and fetuses. Other genetic sequencing is done to improve medical efficacy such as looking at the particular mutations involved in cancerous cells to chose the most effective treatment. Carrier screening is also done of prospective parents to see if they have deleterious traits which could be expressed in offspring. For example, the siblings of those with some diseases such as cystic fibrosis may carry genes for those diseases that can be passed on to their children. They may have genetic testing to guide their reproductive choices. 

Finally, beyond personal curiosity and direct medical contexts, personal genomics is also a key part of some aspects of medical research. For example, genetic testing to get population level genomic information and also to study rare and unusual syndromes of unknown origin. 

Ethically there is a raft of questions that personal genomic testing raises that we shall turn to next. 

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Over the past decade, there have been several high-profile examples of genetic testing leading individuals to take significant prophylactic action against possible disease. In 2013, for example, American actress Angelina Jolie, had a preventative double mastectomy having found out that she carried the BRCA1 gene which increases the lifetime risk of ovarian cancer up to 60% and breast cancer to 80%. In 2015 she had further surgery to remove her ovaries and fallopian tubes and undergoes extra monitoring to ensure early detection of any cancer should it arise. As our knowledge of the genetic risk factors for various cancers grows, such testing is likely to become more common place and raises the question—would you get tested for a disease risk if you could?

Jolie’s choice to undergo testing for the BRCA genes and then to respond with preventative surgery reflects a common view that it’s best to nip disease in the bud and that knowing about a risk of disease is always a good thing, but genetic testing offers some reason for pause on that maxim. Whilst in some cases genetic testing provides information to individuals via which they can reduce their risk of disease, such as for BRCA1, this is not always the case. Not all genes we can test for are what is called “actionable”. For example, if you have a positive test for Huntington’s Disease, there is no treatment. This is a recessive disease and all those with two Huntington’s Disease end up developing the disease and there is nothing to be done about it. Nonetheless, given that Huntington’s Disease has a relatively late onset, many want to know they are going to develop it so they can plan their lives accordingly. Many, however, would prefer just not to know if they are going to get Huntington’s Disease, or are highly likely to have dementia or motor neuron disease later in life. The burden of knowing is just too much. What do you think? Would you prefer to know that you are going to get disease later in life even if you can’t do anything about it? Or would you prefer just to not know? 

Whilst this is a very real question for those with a family history of these sorts of disease, these sorts of situations where we have definitive genetic tests for a disease, are rare. Typically, the relationship between genes and disease is more complex than this and how best to respond to a positive test is far from straightforward. 

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Most genetic tests provide information about a risk of a disease arising, rather than a certainty. This is because most diseases are the product of a combination of multiple genes and the environment. Whilst we can establish when genes are associated with a disease, their presence in a person’s genome doesn’t give a guarantee they will get the disease. We saw this in the case of BRCA1. It significantly raises the risk of breast and ovarian cancer but not all those that carry the gene will be unlucky enough to get cancer, and not all those that get those cancers have the gene. This is typical of most diseases. For example, there are several genes which have been identified as increasing the likelihood of Long QT syndrome – a heart rhythm condition that can potentially cause fast, chaotic heartbeats resulting in sudden death in some cases. It is frequently asymptomatic and only detected after sudden death. Having the Long QT associated genes increase your likelihood of having Long QT but are not definitive evidence. 

How to respond in such circumstances to a positive test result is often complex and hard to assess. In the case of Long QT genes, for example, the behaviours that can reduce the likelihood of Long QT episodes, such as avoiding some medications and certain types of activities, do not come without costs. Avoiding certain exercises, may for example, carry risks in of itself and it is important to be sure the benefits of avoiding exercise sufficiently outweigh that risk. 

Assessments of costs and benefits also differ between people. Not all people that test positive for the BRCA1 gene will undergo a preventative mastectomy and oophorectomy for example. Given the implications for childbearing, many carriers of the gene choose to opt for greater frequency of mammograms and other screening until after they have had children. Others with a lower risk threshold, might choose to opt for surrogacy or other options rather than delay preventative surgery to bear children. 

Whilst we are not anywhere near the Gattaca dystopia, this all shows there are still gnarly ethical and practical questions that arise from these tests. What, for example, would you do if you had a positive genetic test for a disease like breast cancer or Long QT? What sorts of factors would be important for you in deciding what to do in response to a positive test?

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Whilst all these issues relate to the direct costs and benefits of testing, there are side effects to testing beyond this, mostly relating to who has the right to the information we get from genetic tests. 

Because we get our genetic information from our parents, when we find out information about our genome, it can incidentally inform close relatives of their own genetic situation. For example, if I learn that I have the BRCA1 mutation, it gives my parents and siblings information about their likelihood of also having an increased risk of cancer. This raises an ethical question regarding our obligation to our relatives when it comes to disclosing genetic information? Are we required to disclose? What about if someone doesn’t want to know but will learn incidentally because of your response to your testing? 

What about those beyond your family. There are many that would like to know about the results of genetic tests. Life insurers for example. What access should third parties have to your genetic data? Should you be required to disclose it to life insurers? Should we regulate this to avoid the sort of future where those with certain genes are effective second-class citizens?

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A final challenge we will consider is who owns your genetic information. Whilst most of the tests discussed so far here have been the sorts of tests that are done by medical professionals, there are several issues that arise from direct-to-consumer tests in particular. When you spit in a tube and send it off in the post for one of these tests, you are sending your genetic information to a commercial entity, genetic information that for the most part they add to their ever-growing databases. Whilst they generally offer for you to opt out of your information being included in these databases, most people do not invoke this right, and because of this such companies have some of the largest databases of human genetic diversity on earth. Databases that they then sell for commercial gain. Whilst the genomes in these databases are supposed to be anonymised, there are examples of hackers demonstrating that they could de-anonymise this information.

More disturbing perhaps is that many of these databases are large enough now that they can be used to identify individuals that have not donated their DNA. In a famous case in the United States, police gained access to a commercial genetic database and were able to use a sample of from their crime scene to identify relatives of a murderer and thus indirectly the murderer. Whilst any individual submitting a sample to 23andMe or AncestryDNA may be making a prudent or appropriate individual choice, there are consequences of large numbers of us doing these tests that go far beyond the benign. 

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