I am presently watching yet another excellent lecture from the recent exponential medicine conference, that I have referred to multiple times in the past. This particular lecture relates to the issue of genetics in clinical research studies. The presenter discusses a huge amount of the research that forms the basis of our day to day medical practice. The presenter focuses on a key problem in much of clinical research, specifically that the genetic diversity amongst study participants is incredibly limited.
For multiple reasons that are less critical at the moment, study subjects in clinical research are overwhelmingly of European descent. The immediate and obvious question is why this matters? Why does it matter if I am testing a medication on an Asian, European or African individual? In the past, this question was actually rarely raised. When attending a conference about almost any medical issue, it would be rare for a member of the audience to raise a hand and ask the presenter, what percentage of the study population was Icelandic. Of course, I am not specifically referring to Icelandic individuals as being a uniquely problematic group. My point is that clinical study information rarely concerns itself with the most basic question of whether all medications and treatments work equivalently on all humans, as if their genetic makeup makes no difference to the outcomes.
When a physician prescribes medication, there is a whole range of issues to take into account. One type of medication might not be appropriate for someone with poor kidney function. Another medication might be dangerous to someone with poor liver function. We are aware, today, of a long list of genetic variations that make certain people highly sensitive to certain agents. This is not just about people being allergic to eggs and therefore not being able to receive certain vaccinations. This is about certain individuals having deficiencies, due to their genetics, in certain enzymes. Such people can suffer horrible consequences if they do not watch themselves to avoid, for example, ingesting certain foods.
One of the most well-known problems in doing clinical research is finding patients to become part of studies. Apple recently released a development environment called ResearchKit, which greatly helps with reaching out to the general public and identifying potential applicants for a given research study. This system from Apple does not eliminate all issues related to patient recruitment for clinical research, but it definitely helps.
One of the basic limitations of this system is that, by definition, it is limited to people who own Apple phones. As broadly available and used as Apple phones may be, the iPhone is by no means a commodity item that people purchase on a whim. iPhones are from the most expensive mobile devices on the market, and it is fair to say that owners of iPhones tend to be of a certain socioeconomic group. This type of self-selection already introduces a certain bias into the research. The reality is that no research study is perfect in terms of patient selection, and the trade-off between greater recruitment versus less diverse recruitment might very well be worthwhile in many cases.
Interestingly enough, Israel stands out as an incredibly diverse country in terms of almost every social aspect. The population of Israel is relatively small but reflects significant groups of people from almost every corner of the world. Admittedly, certain groups are less well represented across Israel. There are very few Native Americans living in Israel. Asians are not highly represented across Israel, but in fact they are by no means an invisible minority. With the recent influx of African migrants, fleeing countries like Sudan, Israel now has yet an additional significant population of individuals who are genetically very distinct from the rest of the population.
Israel has groups who can trace their family trees back to various tragic periods in Jewish history. The destruction of the holy temples were associated with major emigrations to the surrounding nations. There are Jews who can track their family trees back to the period of the first Temple’s destruction, the second Temple’s destruction, the expulsion from Spain, the expulsion from Europe and so on. There are Iranian Jews that can track their history back centuries to the time of the great Persian Empire. It is by no means unusual to find groups in Israel who can speak of millennia of family history. The key is that these families with centuries of history come from geographically distant locations. As such, taking a random sample of 1000 people walking the streets of Jerusalem would most likely yield of very broad range of genetically diverse groups.
Such a genetic spread works in two ways. If one wants to test a medication on a truly divergent group of people to see if its effect is universal, then Israel can be the ideal research site. Contrarily, if one wants to find a significant number of people with a very specific type of shared genetic background, once again, Israel can be the ideal place.
Over the course of just the last few years, there has been a huge increase in the amount of research and funds dedicated to human genetics. It is now possible to sequence an entire human genome in a fraction of the time and money it cost just a few years ago. And it is expected that in the few years to come, genetic sequencing will become, for all intents and purposes, a commodity item not much different than a pregnancy test. In the midst of this biomedical tsunami, I would humbly suggest that worldwide research groups join together with Israeli partners in order to find the specific genetic groupings that are far more difficult to find elsewhere in the world. Admittedly, the clear majority of people in Israel are Jewish and that of course also reflects in the genome. Nevertheless, one only needs to stroll down to the Western Wall on the Sabbath or especially one of the major holidays, to realize just how many unique genomic lines are being represented in such a small place.
It is said that one of the signs of the time of Messiah will be when the countries of the world look up to Jerusalem and say, look upon these unique and special people and their G-d. One could legitimately argue that G-d has a clear interest in bio-genetics and has created the ultimate environment for curing the ills of the world, all here in His chosen land for His chosen people.
Thanks for listening