Precision medicine for understudied populations

by Roxana Daneshjou, guest contributor

Precision medicine, which leverages a patient’s genetics to help make medical decisions, has the potential to revolutionize medicine. Its applications are numerous: from predicting who may have an adverse reaction to a medication, to allowing targeted therapies of cancer with particular mutations. In 2015, President Obama’s State of the Union announced an initiative to further our understanding of precision medicine and to build the infrastructure to implement it. An important part of this initiative is building a large diverse research cohort to help discover disease-gene and drug-gene associations. The key word is diverse – because genetic risk factors can be population-specific. In the past, individuals of African, Hispanic, and Middle Eastern ancestry have been understudied. Only by including individuals from all different ancestral backgrounds can we hope to implement precision medicine in an inclusive way.

In 2011, Russ Altman’s research group was pondering the importance of inclusive precision medicine when it became clear that several studies examining the baseline genetic variation across the globe, 1000 Genomes and the International HapMap Project, had an underrepresentation of Middle Eastern populations. As a scientist of Iranian descent who had undergone direct-to-consumer genotyping with 23andMe, I wondered how to make sense of my data when no baseline genetic study of the Iranian population existed. When scientists Dr. Mostafa Ronaghi and Dr. Pardis Sabeti approached Dr. Altman’s group about the idea of creating such a baseline, I was immediately interested. Through the generous support of the PARSA Foundation, we began our journey to create a genetic baseline of the Iranian population.

Our first roadblock appeared when we spent months exploring the feasibility of collecting samples in Iran. Due to the economic sanctions at that time, it turned out that establishing a collaboration with an Iranian university and collecting samples there would be nearly impossible. In the United States, however, the Iranian diaspora has created a sizeable population generally representing the diversity of sub-ethnic groups in Iran.  We turned to this population to collect our samples and conducted high coverage sequencing of 77 healthy individuals. This data can be used for answering some questions about the population’s history and also as a baseline for scientists interested in studying disease in this population.

Since our aim is to enable other scientists to answer important questions about disease risk and treatment in individuals of Iranian ancestry, we are committed to sharing our data. Our website, irangenes.com, already has summary data of population level genetic variants. We’re currently working on uploading all of our genomic data on a secure server so that scientists can submit proposals to use our raw data.  Since the sanctions on Iran were lifted in January 2016, we have corresponded with scientists in Iran who are using our summary data to help advance precision medicine there. We are also working on uploading all of our genomic data to a secure server as a part of the precision medicine initiative so that scientists can submit proposals to use our raw data.

In addition to the medical applications, we were also interested in learning more about the Iranian population’s history through its genetics. Based on our data, the Iranian population is genetically distinct from other Middle Eastern populations. However, it is important to remember that any two humans share 99.9% of their genome. Moreover, as has been seen in previous studies in other populations, the different Iranian sub-ethnic groups have a lot of genetic overlap. Though capturing the breadth of human genetic diversity is important to inclusive precision medicine, these studies also show us that – at our core – we are a singular human family.

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Roxana Daneshjou is an MD/Ph.D. student at Stanford and is supported by the Paul and Daisy Soros Fellowship for New Americans.

A better organ-ized kidney solution: Q&A with Sigrid Fry-Revere

Sigrid Fry-Revere, Founder and President of the Center for Ethical Solutions, discusses issues around organ transplantation policy and provides an inspiring and cost-effective living organ donation solution from Iran. We learned more about her work and vision.

Sigrid Fry-Revere discusses living kidney donation solutions at TEDMED 2014 [Photo: Sandy Huffaker for TEDMED]
Sigrid Fry-Revere discusses living kidney donation solutions at TEDMED 2014 [Photo: Sandy Huffaker for TEDMED]

What motivated you to speak at TEDMED?

I was terrified of the thought of speaking before so many people, but I knew my research in Iran and experience as a rejected living organ donor could save lives.

What impact do you hope the talk will have?

We need to rethink conventional paradigms used for donor kidney shortage. Increasing the proportion of cadaveric kidney donation, while helpful, will never be enough. And, as it relates to living donation, it is not simply a question of whether we allow only altruistic (non-compensated) donations or whether we allow a market. Neither a market system nor pure altruism are necessarily the answer, however compensating living organ donors so that they don’t suffer financial consequences for their altruism is certainly a start. Assisting donors with meeting their expenses, or expressing gratitude with gifts or benefits does not diminish their altruism. Unfortunately, policies that limit efforts to to ensure fiscal health of donors makes taking part in the act of helping friends and family who need transplants a privilege only the wealthy can afford.

What’s next for you?

I want to to spur discussion and change, and to this end, I founded two organizations. Stop Organ Trafficking Now! is lobbying Congress to pay more attention to living organ donation and the rights and needs of those living organ donors. Making living organ donation easier means fewer Americans will brave black market organ trafficking channels to try to save themselves or their loved ones. I also co-founded a charity based on my experiences in Iran. The American Living Organ Donor Fund (ALODF) is a living organ donor support organization that provides information, an online donor support group, and financial assistance with non-medical donation related expenses. ALODF exists to support all kinds of living organ donors – kidney, liver, bone marrow and others – but to date only kidney donors have applied. My research has given me a good idea of what needs are alleviated for Iranian living donors in order to to ease the burden of donation. We lack such data for other countries, including our own, so I intend for the ALODF’s efforts to include learning more about the needs of American living organ donors. The American Living Organ Donor Fund has already made more transplants possible for U.S. citizens in its two and a half month existence than some government funded Organ Procurement Organizations (OPOs) average per month. How is this possible? For one, OPOs focus almost entirely on retrieving organs from deceased donors. Cadaveric organ retrieval is expensive and far less productive than live organ transplants. OPOs receive on average $50,000 per kidney retrieval, and as many as 20% of those organs are not viable for transplant. In the last two and a half months, the ALODF has helped 30 Americans receive transplants by helping their living organ donors with out-of-pocket expenses, spending on average $2,500 per donor. If you do the math, that is twenty times less per transplant than what an OPO receives per transplant.

Any corrections to your talk since you gave it?

In both my book and my TEDMED talk I mention that the Fars Province in Iran (an area surrounding the city of Shiraz) doesn’t allow compensating donors beyond the federal government contribution given to all living donors to help cover expenses. Dr. Malek-Hosseini, the head of the transplant program in Shiraz, Iran, notified me in November 2014 that his province no longer allows any unrelated donors. He believes this will  help prevent the illegal payments or black market sales or kidneys that were occurring in his province. Note, no other region in Iran that I know of has banned paying donors or placed such restrictions on relatedness of donors by blood, adoption, or marriage. However it is important to note that throughout Iran, it is illegal for foreigners to either buy organs or sell organs to Iranian citizens.