A vast and entire ideology has been created in which DNA is the Holy Grail and what we are, and become, is a mere unfolding of our genes. People from most cultures, both old and new, have a tendency to place immense faith in this dogma.
In India, where social determinism runs deep and acceptance of the inevitability of all events is bred in homes and temples, belief in genetic determinism often complements or becomes a proxy for fatalism. Here one is told that behaviours, diseases, attitudes and mindsets run in families. Indeed, similarities reproduced in familial mores (interpreted as being genetic) are celebrated as part and parcel of family affection and values. Therefore predictive genetic testing, just beginning to be made available in India, is sure to have a huge market in many different income groups.
In an ironic twist, the credence given to our clannish connectedness seems to be spawning a very individualised form of medicine, one in which each person's DNA is tested or even fully sequenced. The reasoning is that once we have this information, the person (or even the DNA) can potentially be treated early for the all the diseases that might be unleashed on her in the course of her life.
Thus far, paternity tests are the most popular genetic tests in India, but they are quite unlike predictive testing for diseases. Predictive tests forecast the chance that a person will develop a particular disease. These are already becoming popular in India in particular contexts, for example in genetic counselling in some communities before marriage. In the near future one might expect a boom in predictive testing and direct-to-consumer marketing of such tests if India follows a trajectory similar to that found in many other countries.
The ease of rapid and cheap DNA sequencing is ushering in an era of personal medicine that will be quite unlike what we have seen so far. Genetic information is coupled with the ability to store, search, match and retrieve large amounts of data easily because of advances in computer technology. These raise a number of concerns regarding civil rights and liberties beyond just the quandary of finding a way to test the validity and value of predictive testing.
However, let us first retrace our steps by starting with the science.
As in all species, for any given gene, mutations with harmful effects almost always occur in low frequency. Specific genetic diseases are therefore rare and genes do not account for most of human ill health. Given the cost of diagnosing and genetically repairing any single disease, there is no realistic prospect of genetic fixes as a general approach for this class of diseases. There are exceptions, of course, such as sickle cell anaemia and conditions associated with other abnormal haemoglobins, in which a significant fraction of a population may be affected. These persons might be considered as candidates for gene therapy, but long-term success with gene therapy has not been demonstrated and seems unlikely.
Understanding the percentages
As Professor Richard Lewontin from Harvard University has pointed out, for most diseases that represent the largest fraction of poor health and for which some evidence of genetic influence has been found, the relation between disease and DNA is far more complex and ambiguous. Claims for the discovery of genes for complex diseases, such as schizophrenia for instance, have repeatedly been made and retracted.
Genetic tests deliver uncertain probabilities rather than clear-cut predictions of disease. Even in the most definitive genetic conditions, which are few in number, there remains a wide variability in the timing of onset and severity of clinical symptoms.
Most major common diseases such as heart disease, cancer and diabetes do not have a genetic pattern of causation. They appear to be the result of a combination of numerous rare mutations, changes to the normal sequence of nucleotides in a DNA sequence, along with the interplay of other factors. This is what the science has been telling us for quite some time. Nevertheless this reality has been ignored both by business and many scientists.
The euphoria after the sequencing of the human genome led to the establishment of deCode Genetics and, more recently, other companies such as 23 and me, that look for associations between genetic mutations and disease. Recently deCode, the Icelandic firm, went belly up and filed for bankruptcy. The company was using the detailed medical records of Icelandic people along with their genealogical information to learn more about mutations and their accompanying diseases. While there are many business reasons that contributed to deCode's collapse, the complexity of how genes function is believed to be the main cause.
Unfortunately, people will happily spit into a tube and send in their DNA for tests to learn the probability that they will come down with one disease or another. And quite often the results will be ambiguous, trivial or wrong. For example, a person might be told that she has a 20 per cent chance of developing Alzheimers and a 10 per cent chance of diabetes. What do these numbers mean and how can anyone translate them into useful action? More than that, the test may not be valid as it tries to establish a tenuous link between a sequence and a disease, and if valid, the information may not add value.
Most common diseases cannot be predicted with a useful degree of confidence. Indeed, as my friend says, a tape measure, a weighing scale and a person's diet may be far better tools for predicting her or his future health.
The assumption is that more information and more choice are always helpful. But more information does not necessarily change a person's behaviour as we know from what we have been told about the value of nutritious meals, giving up smoking or engaging in regular exercise. People continue to chow down at their local junk food haunts and consume massive quantities of (nutrient-free) white rice, sugar and salt - all known to be bad for one's health. Obesity has been going up and the incidence of diabetes is rising across income groups in India.
So genetic tests in a fatalistic society may even backfire. If you were to tell someone he has a very low risk of heart disease, he may change his lifestyle and invite disease, just as if you were to tell him he has a low risk of lung cancer, he may increase the number of cigarettes he puffs each day. Long-term studies on the impacts of genetic testing on decision-making and behaviour still need to be done.
The risk of discrimination
If the chance of a serious genetically induced disease were higher, such as in the case of Huntington's, a person might be more willing to plan his/her life accordingly. In the case of serious health conditions, genetic counselling should accompany the testing. Thus mail-in tests, and Internet-based diagnosis can be dangerous. Even so, people who are afraid of discrimination if they were to be diagnosed with a disease-causing gene may want to keep their genetic test result information private.
This brings us to the importance of having legislation that will prevent discrimination based upon genetic discrimination. The Council for Responsible Genetics has documented as many as five hundred cases of genetic discrimination. [Disclosure: I am a former President of this Council and continue to serve on the board]. When employers have access to medical/genetic information, it may be used to discriminate against their employees.
One example is the discrimination faced by workers in the Burlington Northern Santa Fe Railroad Company, which was found to be conducting genetic tests on its employees without their informed consent. Tests were carried out to thwart workers compensation claims for job-related stress injuries that caused Carpal Tunnel Syndrome. As an interesting aside: Carpal Tunnel is not an inherited condition, but this did not stop the company.
In 2008, the U.S. passed a law called the Genetic Information Nondiscrimination Act (GINA) that prevents discrimination by employers and insurance companies on the basis of genetic information. An employer cannot use such information for hiring, firing or promotion and an insurance company cannot use it to deny insurance. The legislation was supported both by biotech companies and civil society groups as the former did want the public to refrain from testing for fear of discrimination. This has paved the way, for better or for worse, for personalised medicine.
GINA does not address all possible forms of genetic discrimination. For example, it does not address life insurance, disability insurance, or long-term care insurance and it does not protect persons showing symptoms of disease. It is though an important first step in the fight against genetic discrimination. Thus whether this technology will be useful or add value, we need to protect people from those who will discriminate using it.
This implies that as a first step we need an Act similar to GINA in India in the very near future. We also need clear guidelines and regulation of the budding genetic testing industry so that people are not hoodwinked into carrying out useless tests and can receive guidance from counsellors in the case of serious conditions.
Given the quagmire of public health concerns that need to be addressed in India, the issues around genetic testing and personalised medicine may appear to be remote or even esoteric to some. But we are a country of many economies and capacities. A small fraction of the population is tens of millions. Besides, once a medical approach is accepted, its use tends to spread across the population and income groups. We therefore need to start preparing for the advance of personalised medicine in very concrete ways.