A CRISPR World

Every once in a while, scientists make a phenomenal discovery that truly transforms their field.  For biomedical research (and therefore for the world, as I like to think), no recent discovery has spread as fast and as widely as the CRISPR/Cas9 method of gene editing (making precise changes to specific regions of DNA). This technique is currently so popular that it has scientists and non-scientists alike genuinely interested in its prospects in terms of improving research and healthcare. Being the resident family biologist, I often get asked what all this “crispy” talk is about (note to my dear brother: the joke is only funny once!). Here is my standard introduction to this future Nobel prize-winning technology:

For several decades, scientists have studied the function of specific regions of DNA by causing damage to those regions and examining the effects of the damage on individual cells, organs or the whole organism. While methods used for these kinds of experiments have been improving steadily, the discovery of the CRISPR/Cas9 system is a huge leap forward. The CRISPR/Cas9 system was first identified as a natural method by which some bacteria protect themselves from other microorganism, such as viruses, which attack by injecting their DNA into the bacteria. Without getting too technical, there are two parts to this system: the CRISPR (clustered, regularly interspaced short palindromic repeats) complex, which can recognize a specific sequence in the foreign DNA and bind to it, and Cas9 (CRISPR-associated protein 9), a protein which destroys the foreign DNA by cutting it up, keeping the bacteria safe.

In the lab, scientists can modify this system to target and cut specific regions of DNA in any organism. When a cell’s own DNA is cut, though, its natural response is to try to fix the damage. However, the ways by which these cuts are fixed are not perfect, and mistakes are often made where bits of DNA are added or left out of the fix.  This disrupts the function of the targeted region of DNA, and researchers can then observe the result of these mistakes to learn more about the function of the affected region.

Why all the fuss about CRISPR, you ask? From first-hand experience, CRISPR is significantly more accurate and efficient than previous techniques. To illustrate, the difference between some existing methods and CRISPR is like the difference between asking a six-year-old to find and correct a single spelling mistake in an encyclopedia, and giving the same task to an English professor. Another significant advantage of this system is its adaptability. CRISPR success stories have been reported for organisms ranging from fungi to fish, which is why scientists are universally excited about it. Moreover, the components of the system are cheap, easy to get, and easy to use, making it a viable option for almost any lab. Being able to disrupt a region of DNA is great, but the system has further been modified  so that researchers can also increase, decrease or even change a gene’s function almost at will, and herein lies the immense power of the CRISPR/Cas9 system.

CRISPR/Cas9 technology is so enticing, however, that this sometimes sends scientists down its path when other methods may actually be better for a specific experiment. Sadly, if journal and grant reviewers want to see CRISPR, then CRISPR you must use. Also, the CRISPR system is not flawless, and there are concerns about damage being caused to other sections of DNA that were not targeted.  Moreover, as everyone jumps onto the CRISPR bandwagon, overenthusiasm to publish findings whether for or against the use of CRISPR technology makes room for some sloppy science.

If you’re not in biomedical research, you’ve probably still heard about how scientists are going to use CRISPR to make designer babies and genetically modified foods that will either save or kill us all. How true are these claims? Well, CRISPR does make gene editing much easier, meaning that some things that were not feasible before are now possible. For example, some success has already been reported in using CRISPR technology together with IVF (in vitro fertilization) to fix a heritable disease in human embryos. This application of CRISPR technology is still in its preliminary stages, and we cannot expect that it will bring about an end to all genetic diseases as CRISPR is most useful under specific circumstances. However, for potential parents who are carriers of, or even affected by a heritable genetic disease, this technology  brings to them the hope of having a healthy biological child. How do we define “disease”, though, and when does something go from being a disease to just an undesirable trait? Where do we draw the line, and who draws that line? Does a government or regulatory body have the right to decide for everyone? I don’t know if anyone has the right answers to these questions or any others that will come up as this technology further improves. However, as with all other major advances in science, we must expect and trust scientists to thoughtfully weigh the ethical questions behind their work, and to act in the best interest of humanity.

Big advances in science are always exciting, and from all indications the CRISPR/ Cas9 technology still has numerous uses which we haven’t even begun to study. Thus, until the next big discovery rolls along and takes the world by storm, everything’s getting a little CRISPR.

Beyond Nature

My three girls look nothing like me. Whether or not this will change over time is an open question, but for now they are three different versions of their father. From time to time, though, as I watch them grow, I catch glimpses of myself in their behavior and even in their tastes in food, and this makes me wonder what other aspects of myself lie within their DNA. Our understanding of how DNA (deoxyribonucleic acid) works is improving everyday as new research findings are published, and as researchers link disease after disease to specific genes, I can’t help but worry that I may have passed on something harmful that will show up at some point in their lives. Luckily, the story of life is more complex than just DNA.

For many centuries, long before the discovery of DNA, psychologists and biologists alike have debated over how much of who we are is controlled by the environment. This “nature versus nurture” debate has now gotten much more intricate as it has expanded to include the influence of external and internal environments on how our DNA is read and interpreted by our bodies. With all the new information available to us today, it is easy to focus on the genetic basis of life. However, studies looking at the links between our DNA and specific conditions make it clear that the role of our environment cannot be overlooked. For example, recent research shows that about 50% of the factors that influence intelligence are inherited. This means that half of the factors controlling intelligence are NOT inherited. In fact, it has also been shown that especially for children, education, nutrition, and even a peaceful, nurturing home environment all contribute to intelligence. Similarly, the heritability of depression is at about 38%, meaning that 62% of factors leading to depression are under the control of our environment.

Several studies conducted on the heritability of diabetes put this number between 25-80%. These same studies are quick to point out, however, that the effects of genetics versus those of living in the same environment are not completely separable.  Researchers agree, though, that the interplay between the environment and genetics is crucial to the development of this condition. Similarly, interactions between genetics and the environment are responsible for heart disease and   asthma. Obviously, there are some illnesses that are purely inherited, and knowing your family history is important as it tells you what conditions you may be at an increased risk for. Still, it is nice to know that by trying to live a healthier life physically, mentally and emotionally, I can influence whether or not I develop certain conditions and to what extent.

What, then, is my most important contribution to my children’s lives? Probably not their DNA. Creating a healthy environment for them to grow and thrive, helping them develop good eating habits, teaching them to value themselves and others, and to be kind, and showing them that they can make a difference in the world are all just as important, if not more important than genetics.  Our DNA is an inheritance given to us without our consent, one which we pass on to our children without asking for permission. Luckily, we have a significant amount of control over the external factors that influence our make-up, and we can help build the best versions of ourselves, and of our families, upon the foundations laid by our DNA.

Back to the Bench

I have been surrounded by science from the day I was born. I grew up with a father who would answer my simplest childhood questions with elaborate scientifically-accurate descriptions, and though most of his efforts were sadly wasted on my younger self, I learned that there was a fascinating world out there just waiting to be explored. When I was a little older, I would spend hours reading my brother’s high school biology text book, captivated by descriptions of animal development. One of my happiest days was when that book became mine, and I no longer had to sneak around to read it. Biology has always been my main interest, and I pursued this through graduate school and to the postdoctoral level. Less than two years into my postdoc, however, I found myself with two adorable babies in my arms and a fellowship that would not cover the cost of childcare. For the first time in my life, I turned away from science as my new loves took precedence.

Surprisingly, I found out that it is quite common for women in the sciences to step away from their hard-earned careers to focus on their families. Also common is women taking less research-intensive (and therefore less time-consuming) jobs to improve their work-life balance. According to the United Nations Educational, Scientific and Cultural Organization (UNESCO) Institute for Statistics, an average of 53% of undergraduate students worldwide are female. However, only 44% of doctoral students and 29% of career researchers are women.  Should a woman be able to decide that she would prefer to be home with her kids? Absolutely. Should such a decision be forced upon a woman because of lack of support from her workplace? Absolutely not. If a profession that relies so heavily on ingenuity to make progress is losing a significant percentage of its workforce, can you imagine how many questions relevant to our health, the treatment of diseases and the advancement of science are going unanswered?

Fortunately, many institutions are catching up to the times and providing, or at least attempting to provide, support for scientists who just happen to be parents. In the United Kingdom and Australia, the Athena SWAN charter sets guidelines for institutions trying to close the gender gap in the sciences, among other fields. This charter makes several practical suggestions to improve work-life balance, such as limiting work activities to business hours so that parents can participate in all official events.  Recently, some government funding in the UK is being tied to institutions following the guidelines set by the Athena SWAN charter, and this has been a big incentive for organizations to speed up their progress in dealing with matters of gender equality.

The American Association of University Women (www.aauw.org) has been committed to supporting women in academia for over a century, and has over the years expanded its focus to include women and girls at all stages of scientific discovery. The AAUW provides funding for science education and research, does advocacy and public policy work, and even conducts salary negotiation workshops so that women are ready to demand fair wages when they get a job offer. UNESCO has also set up several initiatives to support women in science, including teaming up with the L’Oréal Corporate Foundation to recognize women excelling in their fields and to provide awards to fund their research.

Some institutions and foundations have from time to time asked focus groups to help identify areas of support for women. One particularly interesting suggestion is that institutions should allow researchers who become parents to use funds from grants to pay for childcare or to hire extra help in the laboratory if needed. Several institutions are also adopting policies that allow both women and men to take a total of one (unpaid) year off to take care of family commitments. The landscape for women in science is gradually changing. 

My stay-at-home-mom years were short-lived, though, and now with three little girls I found my way back to the bench. I have found that with children waiting at home, I can’t work late nights or weekends, and my vacation schedule is controlled by whether or not my children’s daycare center is open. I may not be able to work the long hours that I used to, but now I make every second count. I find that I am better at planning my experiments and more efficient at carrying them out, though sometimes this means skipping lunch on particularly busy days. I am relieved to find that while my priorities have changed, my love for research has not. I used to walk around the lab with experiments on my mind and a song in my heart, and that is still true. But now, from time to time I suddenly break into a smile when I remember something one of my daughters said. Granted, biomedical research is interesting, but having a 3-year-old say “Mummy, can you kneel down so I can ride you?” is priceless.