Biology students pursuing a Ph.D. tailor their academic lives around getting published in top journals. For Sonia Vallabh and Erik Minikel — a husband-wife researcher team pursuing a Ph.D. programme at Harvard-MIT Broad Institute — it’s almost a life-and-death situation.
Every research advance they make is hope that Ms. Vallabh can stave off death from a fatal genetic disease, like the one which killed her mother. Before beginning to train as biologists four years ago, Ms. Vallabh and Mr. Minikel were a lawyer and transport planner respectively.
The unexpected death of Ms. Vallabh’s mother, an Indian, from Fatal Familial Insomnia (FFI) — a one-in-a-million hereditary disease that results from a malfunctioning protein that degrades the nerves, causing a relentless insomnia and eventually death — made Ms. Vallabh take a test only to learn that she had inherited the same malignant version of the gene from her mother.
Earlier this week, the couple published a paper in Science Translational Medicine, reporting that not all versions of the gene that cause so-called prion diseases such as FFI are harmful. Prion diseases are a class of ailments that afflict humans as well as animals. ‘Mad cow disease’, for example, is a prion disease that can affect bovines and can be contracted from eating infected meat.
The duo’s research found that it’s still possible to inherit a prion protein gene and not fall sick, but even more significant is the process they followed to find this out. Mr. Minikel and Ms. Vallabh searched databases of genes of about 16,000 people with prion diseases and compared it to gene data sets from nearly 60,000 people without prion diseases who’d consented to make their data available through genome-analysis companies such as 23 and Me and university databases. Unfortunately, the version that Ms. Vallabh carries — the duo reconfirmed — is still malignant.
In an e-mail interview with The Hindu , Ms. Vallabh and Mr. Minkel said that even against the odds, both were as fired and passionate about looking for drug targets to cure prion diseases.
Excerpts:
Most researchers, in the early stages of their career, would be elated about getting published in a top journal. Your study gives hope to some prion patients that they wouldn’t fall sick but you’ve got renewed confirmation that you carry a fatal version of the prion gene. How do you react to that?
Sonia Vallabh (S.V.): Publications in top journals really aren’t the point for us… We are here to move the ball forward on treating the disease, and everything else is only a means to an end. I reserve my elation for the signs of progress in our and others’ therapeutic development efforts.
The arc of sadness/happiness isn’t what we’ve experienced. There has long been strong evidence that a number of PRNP (prion protein) variants, including mine, are highly penetrant [or pass into subsequent generations] and that is why we are committed to working on therapeutic development and have been, since long before this study. I’m happy that this work clarifies the risk spectrum and delighted that it changes the prognosis for some individuals, but we weren’t pinning our hopes on it changing mine.
How old are you? As scientists, have you calculated the odds of whether you will be able to develop a medicine in time to stave off or cure prion disease?
S.V.: I’m 31 and Eric is 32. We are here to accelerate therapeutic development and based on the outstanding foundation of basic science knowledge that the prion research community has been building for decades, since long before we came along, we believe that meaningful advances will be possible in my lifetime.
How satisfied are you with the quantum of data being shared between companies, individuals and hospitals. What is still required?
S.V.: Private donations built the Broad Institute, which has made everything we are doing now possible. Private donations to Prion Alliance [an organisation founded by the couple to collate funds, information and research on prion diseases] in particular do not compare with the [U.S.] National Institutes of Health grants in terms of supporting work in the prion field. But, we are showing that targeted donations of any scale can be catalytic and deeply meaningful.
The culture of sharing in science has a long way to go, but I like to think this is a sign that we are moving in a great direction and living and working at an exciting time.
For individuals, I think that genetic information can still be scary to even obtain yourself, let alone share openly. I think a large part of this is just the newness of genetic medicine and people being concerned, understandably, about the unforeseen repercussions that genetic information could have on their life. I hope that as a society we can begin working to build a culture that is supportive of people seeking out information, if they so choose, that can help them understand and potentially improve their health.
Does this study have implications for Indian populations?
Erik Minikel: The data sets that we have looked into don’t have specific insights for India. So Indians are no more or no less susceptible to prion diseases than other groups.
jacob.koshy@thehindu.co.in
