Engineering Babies One Crispr at a Time

 

By Sophie Balmer, PhD

Over the past few weeks, the scientific community has been overwhelmed with major advances in human embryonic research. Whether researchers report for the second time the use of Crispr to edit the human germline or extend the conditions of in vitro culture of human embryos (also here), these issues have been all over the news. However, as all topics can not be raised in only one post, therefore, I will focus on genome editing studies.

 

About a year ago, one research group in China reported the first genome editing of human embryos using Crispr technology. Although these embryos were not viable due to one additional copy of each chromosome, this study quickly became highly controversial and raised strong concerns. The public and scientific communities questioned whether editing the human germline for therapeutic benefits was legitimate, leading to numerous ethical discussions. A few of weeks ago, a second study reported genome editing of embryos reinforcing the debate around this issue. Additionally, several research proposal involving genomic modification of healthy human embryos’ DNA have been validated recently in other countries. In this post, I want to address several questions. What are the possible advances or consequences of such work? What is the current legislation on human genome editing worldwide? Are these studies as alarming as what is written in some newspaper articles?

 

The emergence of the Crispr technology a few years ago has revolutionized the way scientists work since this method greatly improves the efficiency of DNA alteration of model organisms. However, this powerful tool has also raised many concerns, notably on the possibility to easily tweak the human genome and generate modified embryos.

In the eyes of the general public, this kind of experiment resonates with science fiction books or movies. Because of the high potential of this technique, it is crucial to inform everyone correctly to avoid clichés. Recently, one of my favorite comedian and television host John Oliver depicted in a very bright and amusing way how small scientific advances are sometimes presented in the media. Although the examples he uses are dramatic, every scientific breakthrough gets its share of overselling to the public. In the case of gene-editing of human embryos, pretending we are about to use eugenics principles to engineer babies and their descendants with beneficial genes is pure fiction. However, to prevent any potential malpractice from happening, clear ethical discussions and regulations need to be established and then explained to the public to prevent misunderstanding of these issues.

Within the scientific community, last year’s results triggered the need for new discussions and regulations on human cloning. Modifying the genome of human embryos involves modifying the germline as well, leading eventually to the transmission of the genetic alteration to future generations. However, the consequences of such transmission are unknown. Potentially, this could resolve a number of congenital genetic diseases for the individual him/herself and be used for gene therapy but would result in generations of genetically modified humans.

 

Because of cultural and ethical differences between countries, the legislation (if there is any) around working with human embryos or cells derived from human embryos (hESC for human embryonic stem cells) is variable. International ethical committees have only been able to establish guidelines as instituting international laws on human cloning is impossible. Ultimately, each country is responsible for enforcing these rules. Most countries and international ethics committees agree on a ban on reproductive and therapeutic human cloning. Moreover, following last year published experiments, a summit held in December 2015 gathered experts from all around the world. The consortium concluded that gene-editing of embryos used to establish pregnancy should not be performed (for now) and to follow up on all-related issues, new sets of guidelines are coming out imminently.

 

Still, it seems difficult to get an idea of the consensus depending on the countries in which scientists perform experiments. There is range of possibilities when working with human samples: some countries completely prohibit any manipulation of human embryos or hESC while others authorize genetic modification of the embryo for research purposes only under specific conditions. In between several nations authorize research exclusively on already derived lines of hESC and others authorize derivation of hESC but no manipulation of the embryos themselves.

Besides these general rules and as of today, three countries have approved proposals for gene-editing of human embryos: China, the UK and Sweden. Research proposals in both European countries have authorized Crispr targeting of specific genes in healthy human embryos to assess the function of these genes during early human development. However, these embryos can not be used for in vitro fertilization (IVF) and have to be destroyed at the end of the study. The purpose of these studies would be to confirm what has been described in hESC and in mammalian model systems and contribute to our knowledge of human development.

 

On the other hand, both published studies from China focused on Crispr targeting towards clinical therapies of an incurable blood disease or HIV. The overall purpose of such projects is to test the use of the Crispr technology for gene therapy. Although rendering embryos immune to several diseases using Crispr is an attractive possibility, it seems more urgent to probe the validity of the technique in humans and assess whether the mechanisms of human embryonic development are similar to what has been hypothesized. Gene therapies have already been successfully attempted in humans using other techniques to modify the genome. Yet, the modifications were targeted towards specific cells in already-born individuals. Again, modifying the genome of embryos implies that the mutation will be inherited in future generations and is in a large part the reason of this debate. Moreover, Crispr targeting still leads to unspecific modification of the genome, although very promising results show that newly engineered cas9 could lead to very specific targeting. The consequences of such off-target modification are unknown and could be disastrous for the following generations.

 

Overall, no research proposal dares to consider genetically modified embryos to establish pregnancy but as research moves faster, increasing demand for ethical discussion and regulations are brought forward. As more studies come out, it will be interesting to follow the evolution of this debate. Additionally, informing clearly the population of the possibilities and outcomes of ongoing projects should be a priority so that they can give an informed consent towards such research. In any case, a clear boundary needs to be established between selecting the fittest embryo by pre-implantation genetic diagnosis, which is routinely performed for IVF and playing the sorcerer’s apprentice with human embryo’s

So You Want to Be in… Scientific Public Relations

By Sally Burn, PhD

Scizzle was recently fortunate enough to chat with the infectiously upbeat, super accomplished Cherise Bernard, PhD. Cherise is Senior Manager for Elsevier’s U.S. Engagement Program, as part of their Global Academic Relations team. She acts as a conduit between the publisher and academic institutions and performs scientific public relations duties (in addition to being a “technology midwife”… more on that later). We got the lowdown on the publishing world, what her job entails, and how you too can move into this exciting sphere of work.

 

Hi Cherise! So, what does someone in Scientific Public Relations do?

Basically, my responsibilities align around being a thought leader. When I say a thought leader, one of the primary responsibilities that I have is to build relationships, programs, and initiatives with different US universities. One topic that my company is very passionate about right now is precision medicine. We identify universities in the country that are also passionate about precision medicine and we network with them to understand their challenges. When I say I need to be a thought leader, I need to be having very up-to-date conversations about precision medicine to recognize what the field is lacking and what steps need to be made to propel the field forward. The execution aspect of my job is to make sure that I build relevant programs in order to do those things. For example, let’s say Stanford University is known for its work in precision medicine. What I would do is to go meet with, let’s say the vice president of research at Stanford and then build some program around precision medicine where Elsevier and Stanford are both contributing data or resources, jointly resulting in a better understanding of precision medicine at Stanford and as a whole.

 

What kind of data do you contribute, specifically?

Elsevier is a scientific information solutions company. We publish over 2,500 scientific journals, both online and in print. Not only that, we also provide other digital web-based solutions for the scientific community such as Scopus, Mendeley, and Science Direct. Scientists all over the world use these resources in order to disseminate their research. For example, using our SciVal platform, universities can actually create custom reports indicating what their top research areas are.  How would that be helpful for an institution? This can assist them in making targeted investment decisions for areas that they dominate in. My job is not black and white; there are no two days that are the same. It differs with every single engagement that I’m involved in. But it’s always going to be a mutual exchange of information to promote an extensive learning opportunity or to promote advancement in a particular field or initiative. This should be a really interesting blog post because, honestly, my job is not one that biomedical life scientists have traditionally considered and said, “I want to do that with my PhD.” It’s something that I just fell into. It allows me to use creativity every day. And so far it’s awesome.

 

How did you get this job? What is your background?

I always tell people I’m a recovering scientist because that’s exactly what I am. When I was younger, I knew that I wanted to go into research. That interest led me to major in chemistry as an undergrad. Then I pursued my PhD in Cellular and Molecular Pharmacology, focused on cancer research. Then… I don’t know when there was a shift but somewhere during graduate school I realized that I wanted to see how the research applied more to the patient. I’m at the bench, I’m doing my research but – what happens to the research after it leaves the bench? What is the impact on society once the paper is published? Does it have an effect on the actual patient? It was then that I decided to do a little bit of research myself into the process of taking research findings and bringing it to market. I learned about the field of technology transfer (or scientific commercialization) and began to understand that this is how inventions are translated from the academic bench to industry, then to the bedside. So, with this knowledge, I decided to pursue a mini-MBA certification at Rutgers while in the thesis phase of my PhD program, just to get more of an understanding of what the business aspect of science looked like. Everything that a full MBA would cover, we touched on it in a span of twelve weeks. It was a very intensive program. But I was able to do that at night while still working in the lab during the day. It was extremely difficult but I felt like I needed to get some framework behind what I was interested in doing.

That mini-MBA helped me land an internship with the Rutgers Office of Business Development and Technology Transfer. The internship allowed me to not only learn about the intellectual property process, but also taught me how to evaluate, market, and license new technologies coming out of the university to commercial partners. The commercial partner used the licensed technology in coordination with their own technology portfolio while the university received licensing fees and profit shares from any resulting products. Prior to the internship, this whole concept was foreign to me. As a scientific researcher, no one talks about this really, unless you are in a lab that already has a relationship with a commercial company. I learned that there were technology transfer offices at the majority of universities, commercializing the research taking place at the bench. I was completely intrigued and I knew that I wanted to pursue it further.

My Rutgers internship allowed me to get a paid position at Rockefeller University’s technology transfer office, where I stayed for two years. From Rockefeller, I moved on to Mount Sinai Innovation Partners at the Icahn School of Medicine at Mount Sinai in New York. That’s where the creativity started for me. I was able to align my commercialization experience with my passion for education. The director at Mount Sinai Innovation Partners gave me the creative freedom to build a commercialization internship program. From that opportunity, I was also able to build other programs, educating the Mount Sinai community about entrepreneurship and scientific communication. Mount Sinai was the place where I learned that I could think like a scientist but I could also be creative. That whole concept was foreign to me because as a scientist you follow protocols. You read papers. You see what other people have done. The whole concept of creativity, of building things right from scratch not knowing what the process will be at all was something that I hadn’t experienced before and now I was. I started realizing that this is exactly what I wanted to do. That experience led me to my position now at Elsevier – so you can see the transition, right? I was able to build programs, initiatives, and learning opportunities at Mount Sinai and now I’m at Elsevier with the amazing opportunity to create on a national level with a portfolio universities and organizations!

 

Do you feel like the mini-MBA was essential for getting to where you are now?

This might seem like a strange answer, but in terms of the content, it was not essential. The content helped. I became familiarized with a lot of business terms. But it was essential in terms of me proving my commitment to learning about this field. I tell PhDs and postdocs this all the time: sometimes you need to make certain moves to push your career forward… and it’s not really so much about what you’re doing, but more about you proving your commitment to identifying your skill sets, learning your personality, understanding what you like, what you don’t like. Everything will not always work. Everything will not always be a home-run. Trust me, I did things that I’m not even discussing here that I was just like okay, no, I don’t want to do that. But I made a decision for myself to always follow my instincts. That’s another concept that I’m actually going to be trying to write a short book about – following your instincts as a scientist and not always staying “within that box” of the norm.

 

You’re outgoing with great communication skills. Would you say those are essential skills in your job?

Yes. Outgoing, being a great networker. But I wouldn’t just say “go network”. I would say do targeted networking. Find the people who you can actually have a great conversation with. Find the people who it’s strategic for you to talk to and it’s strategic for them to talk to you. To do that, you have to do your research. That’s another thing that my PhD taught me, which may be underutilized by other PhDs – you know how to do research. You know how to find stuff out. It doesn’t have to be about a protein. You can also find things out about people. If you make your networking more strategic and have more of a purpose, then follow your instincts, your networking will turn into relationships and that’s the crux of what I do right now – relationship building.

 

Do you think LinkedIn is important for somebody who wants to get into your industry?

Definitely. I think LinkedIn is just important for getting into any industry at this point. I think it’s a great way to initiate cold meetings. If you don’t know someone and have never met them but you would feel they would be beneficial to know, LinkedIn is a great way to introduce yourself. If you are able to then send them a little note, or do your research, find out their e-mail address, find out their phone number, do a cold call. These are the kinds of things that people really need to take initiative on nowadays – really just put yourself out there and don’t necessarily care about how you look all the time. Just put yourself out there.

 

In addition to taking the initiative and networking, do you have any other advice that you would give to someone who wants to get into your field?

The first thing I would advise is to understand who you are. I know it sounds a little bit cliché, but when you are going into a field that’s not very heavily populated, especially by scientists and by PhDs, you have to be extremely sure of yourself and confident (even though the confidence may not be an everyday occurrence!) Know what your interests and passions are. Know what your personality is like. If you don’t like to talk to people, this is probably not the best job for you! My second piece of advice is to read. Read what’s on the cutting edge (this is important for scientists who are interested in technology commercialization as well). What are the hot topics right now? Last year, President Obama did his State of the Union Address and he talked about advancing the fight against cancer. When I listen to that, I’m not just listening to it as Cherise in my living room. I’m also listening to it for work because when I meet with the NSF and the NIH, they are taking their cues and forming their priorities directly from The Office of the President. I need to be well versed so that if I have a meeting at NIH and the NSF, I know what I need to talk to them about. The only way to do that and to be confident in those types of conversations is to be really aware and be on the cutting edge of what’s going on in the country and even globally in terms of scientific research, technology, and data.

 

How do you remain on the cutting edge? Are there any sources of information that you particularly rely on?

I read reputable blogs by thought leaders in the fields that interest me.  I try to stay up to date on articles in Cell, Science, and Nature. They are pretty much always on the cutting edge. And of course, reading the journals that Elsevier produces. It’s also cool because I come from a commercialization background so I am still on top of those kinds of literature too. When you read about startups, they are usually a couple of years ahead of where the rest of the industry is currently. I also read venture capital blogs because their investment decisions contribute a great deal to the technology commercial landscape.

 

What are the top three things on your to-do list for today?

I have a portfolio of programs and initiatives that I’m working on. One of the things constantly on my to-do list would just be e-mailing and phone conversations with colleagues and partners to find out where we are on certain things and to ensure that the plans are moving forward. I spend a lot of time as well reading and understanding the strategic goals of the universities that I’m working with, identifying openings and gaps in their capabilities, and assessing if there’s an opportunity for us to partner with them. I need to constantly track updates and relevant public relations topics happening with our partners and distribute that information to my team. Another item on my to-do list is focused around more logistical efforts. If I have meetings next week on the West Coast, I need to be churning out the agendas for these meetings to everyone on the team. I’m on the thought leadership side but I’m also on the program management side.

 

What are your favorite and least favorite parts of the job?

I guess my favorite part would be the travel because obviously I get to see places that I’ve never seen. Another great thing about this position is that it’s a great work-life balance. I get into the office about 8:00 a.m. every day and I pretty much leave around 5:00, 5:30. Since we’re a global company, it’s also pretty feasible to work from home. My first day here I was given a work cell phone and laptop. So I take work everywhere I can work, especially since I have colleagues that are in Asia – sometimes I have to wake up for 7:00 a.m. calls with them because of the time difference. But I can just work from home if needed. That’s another really cool part that I really love. It’s the flexibility to do that. I also really enjoy the fact that my role is a brand new one, but that’s also my least favorite part! It’s my least favorite only because everything is from scratch. Sometimes that’s a little bit scary because I don’t know if I’m doing something in the right way. Nothing is set in stone and it’s just difficult to measure my success. But that’s also the really intriguing part of my job, too: that I don’t know. I have to figure everything out and that actually motivates me to get up and try new things every day. It’s my least favorite and most favorite part of what I do.

 

Do you miss academia at all?

No, I don’t. Honestly, I get a healthy dose of academia without actually being in it, so I feel like I get the best of both worlds. I still work with academia on a very regular basis so I can’t really miss it. But I’m far enough away from it that I’m not dealing with the politics of it. I have other politics now but it’s not academia politics, which is great. Obviously, there are other benefits to not working in academia like a higher pay range, bonuses… those types of things that academia historically does not offer.

 

How do you see your field developing over the next ten years?

The way that we disseminate research is changing rapidly because of technology, because of social media. I think that in order to make that change amenable to universities, you need some liaisons, the kind that know both the old way and the new way to be there to push that change forward, and I think that’s what I am. In all of the topics that I’m working on [at Elsevier], we are trying to change the face of them, be thought leaders in them because we are trying to go from what’s old to what’s new. I’m like a midwife to push technology forward! All aspects of science will change rapidly within the next ten years, including how we educate and train our professionals and disseminate our findings.  We’re going to have to switch from the bench mentality to what the bigger, more global impact will be. We’re going to have to start changing the way that we educate our scientists, the way that we produce scientists. We’re going to have to change the graduate curriculum to account for the surges in technology that’s currently happening. We’re going have to change the way that we educate medical students to account for artificial intelligence and digital health in medicine. All of these things won’t happen overnight. The field requires these champions that are right in the middle of it to say, “Come on. Let’s go. We know you don’t want to leave this old way but we’ve got to go. We’ve got to move forward.”

 

What kind of positions does someone like you move on to?

I haven’t started thinking about it yet but now that you’re asking me there are a lot of things I can do. I think that I can probably transition from here into leadership roles in academia. I think that vice presidents of research and deans, they really need forward thinking people. They need people who are inventive, creative, and willing to take some risks. That’s possibly something that I could do if I wanted to return to academia. I also see myself being a motivator and public speaker in terms of scientific education, making sure that US universities in particular stay on the cutting edge of educating our scientists. Maybe an education consultant – helping universities switch gears to move their curriculum forward. Then, in terms of publishing, what I’m doing right now has its own ladder as well, because right now I’m a senior manager but I could become a vice president in our Global Academic Relations team.

 

Final, most important question: In the event of a zombie apocalypse what skills would someone in scientific public relations bring to the table?

I would probably be the one trying to befriend the zombies and saying: listen, that zombie right there, he might be able to help us. I’d say I know you guys are afraid of the zombies, but I don’t think all of them are bad. We can’t talk to all of them, but let’s look for one of them that can give us some inside information. I will be the one in the zombie apocalypse to bring all the inside information to the table. You have to be like an advocate for at least one of them because that’s the only way we’ll know what their plan is. I’m all about building strategy and you have to be able to view people as a resource in order build strategy.

 


Cherise can be contacted by email at c.bernard@elsevier.com or via LinkedIn.

 

So You Want to Be an… Equity Research Associate

By Sally Burn, PhD

In this week’s edition of “So You Want to Be a…”, we turn to the financial side of science and find out about a career in biotechnology equity research from Raluca Pancratov. Raluca completed her PhD in pharmacology at NYU School of Medicine, before transferring her analytical skills to the fast-paced world of equity research. Read on to find out if this is the post-PhD career for you!

 

Hi Raluca! So, what exactly does an Equity Research Associate do?

An equity (stock) research associate analyst typically works for large Wall Street investment banks or boutique investment research firms. The associate’s role is to support the senior analyst’s stock recommendations (buy, sell, hold) for investor clients. These can include pension and mutual fund managers, as well as hedge fund managers. Research analysts forecast whether a stock will go up or down and by how much, based on the commercial outlook of the analyzed companies. For biopharma companies, stock performance is often linked to the success of drugs in the clinic and on the market. Given the complexities of the drug development process, advanced degree holders such as science PhDs and MDs are well-positioned to understand clinical data and predict the likelihood of clinical success. A good portion of the work is keeping up to date with the newsflow (scientific, clinical, regulatory, or commercial), which influences day-to-day (and sometimes minute-by-minute) stock value. Estimating the value of a stock entails analyses of financial statements and forecasting the company’s sales and expenses.

 

How did you get to where you are now?

I have always been fascinated by drug development and my PhD mentor cultivated a “bench-to-bedside” mentality in the lab. I also enjoyed working on a translational project. I learned about investment research at one of the many “What can you be with a PhD?” career fairs that I attended (organized by the great team at NYU School of Medicine), where alumni from my graduate program described this type of niche position within finance. I remember thinking “Ah, I could do that!” and proceeded to read as much as possible about the biopharma sector and enroll in finance classes at the NYU School of Continuing and Professional studies. In addition, I conducted numerous informational interviews with professionals in equity research and educated myself on financial modelling. I got my first job through alumni referral, and was fortunate to encounter terrific mentors that trained me how to think about strategy and market “sentiment” driving stocks up and down.

 

What are the key skills needed for this job, and did you develop any of them during your PhD?

First, equity research requires analytical abilities, which I honed during my PhD, designing and troubleshooting experiments. Second, the finished product of an equity analyst is a written note or report, distributed to investor clients. Therefore, written communication skills are of utmost importance. While I wrote papers, reports, proposals, and a thesis during my PhD, their style is very different from the succinct and to-the-point communications required for the equity analyst job, so I had to adapt my writing style. Lastly, I am grateful to my PhD advisor for extensive training on the ins and outs of PowerPoint and delivering presentations, which came in handy in equity research.

 

What would be your advice to a PhD wanting a job similar to yours?

For scientists interested in a career in finance, I would advise reading as much as possible about the current therapeutic landscape and the biopharma industry players, and keeping up to date with translational and medical newsflow. I remember my undergrad colleagues majoring in social sciences spending a lot of time taking classes on designing effective surveys. In retrospect, I wish I had taken some of those courses and I recommend STEM scientists focus on this type of research method. I also advise trying to learn as much as possible about finance and accounting, perhaps by taking advantage of local course offerings in these fields. Some universities have access to published equity research through the local library – I would strongly suggest reading as many reports as possible, in order to become familiar with the writing style and structure of the different investment communications.

 

What are three things you do on a typical day?

On a typical day, equity analysts wake up to news from the European markets and U.S. market press releases begin to trickle in at 7.00am ET, so they need to digest a large volume of information, assess impact to covered stocks, and evaluate if financial estimates will be adjusted. News of a drug succeeding in a Phase III clinical trial may translate into adjustments of the drug’s probability of success. Second, equity analysts spend a lot of time on the phone, pitching and discussing investment ideas to investor clients. Third, equity analysts also coordinate multiple diligence projects, pertaining to products/clinical trials of covered companies or to companies considered for future coverage.

 

What are your favorite – and least favorite – parts of the job?

I enjoy reading and analyzing novel drugs and therapeutic modalities, and learning about the forefront of medicine. There is a great feeling of satisfaction when a prediction or forecast is accurate, when value creating events such as successful drug development are in line with the analyst’s expectations. I also enjoy attending medical conferences in fields as varied as oncology or rare disorders, and getting to know where the field is headed and what the upcoming research directions are. My least favorite part is the constant “on call” feeling, as key news can be announced any minute (including late at night), and the work required to react to major announcements can derail a day’s schedule.

 

Is there anything you miss about academia? What was the most challenging aspect of moving from the bench to equity research?”

Sometimes, the answer to a molecular question can only be found by experimental means (e.g. which strategy is most effective, targeting PD-1, PD-L1, or both in cancer?) and I miss not having the means to answer it directly. I was told before I started that equity research is an effort-intensive job, and believed it would be comparable to lab research (especially paper resubmission season). However, the pace of work is more comparable to the feeling during preparation for an important lab meeting or department presentation. Except for that is the feeling every day on the job.

 

How do you see your field developing over the next ten years?

Biotech and pharma equity research remain niche areas within finance, and the need for freshly-minted PhDs fluctuates greatly. During the recent biotech boom (2012-2015), hundreds of new companies became public, prompting multiple financial institutions to hire more biotech analysts as coverage universes became too big for a single team to manage. However, with more and more analysts covering the same stocks, client revenue is gradually directed at the minority who conduct the highest quality and most differentiated analyses. Over the next ten years I predict a lingering need for specialized professionals to analyze drug data, thereby predicting stock moves. However, in the social media/digital era, many analysts may have to reinvent themselves and the methods they use to reach clients and deliver the results of their analyses.

 

What kind of jobs does someone in your position move on to?

The most straightforward transition is promotion from the associate to the analyst position. To employ an academic analogy, analysts are similar to PIs, deciding on which companies to cover and what the course of the franchise should be, while associates are similar to postdocs, executing most of the analytical work to support such recommendations. Alternatively, associates may go on to work for the so-called “buy side”, investment managers such as hedge funds, pension funds, or mutual funds. This type of due diligence work is highly similar to that done by research analysts working for the “sell side” (i.e. banks “selling” stocks and “buy side” investors “buying” them). In addition, the diligence, market research, and valuation skills are amenable to other positions in corporate/business development and strategy in biopharma, investor relations, and consulting.

 

And finally: In the event of a zombie apocalypse, what skills would an equity research analyst bring to the table?

Man, since we survive the pressure of having to do multiple things on a  deadline – immediately, we can rapidly seize a situation and make a recommendation: Sell! Buy! Erm, I mean Run! Take cover! We may only be correct 50% of the time, but you can be darn sure that our attention to detail (honed from those endless days of Excel modeling) is so great that we’ll avoid those zombies lurking in the shadows.

 

Fighting Zika Virus with Mosquito Genetics

 

By  John McLaughlin

 

The Zika virus burst into the news last year when a dramatic increase in microcephaly cases was reported throughout several states in Brazil. This frightening birth defect quickly became associated with the mosquito-borne virus, carried by Aedes mosquitos; Aedes aegypti, which also carries Dengue, is the main vector in the current Zika outbreak. While Zika virus usually affects adults with fairly mild symptoms such as fever, rash, and joint pain, it can have severe or fatal consequences for the fetuses being carried by infected females. In fact, The World Health Organization (WHO) has recently reported a scientific consensus on the theory that Zika is the cause of the large number of Brazilian microcephaly cases.

 

In January of 2016, a Hawaiian baby born with microcephaly became the first case of Zika reported in the United States. And the U.S. National Institute of Allergy and Infectious Diseases has recently stated that a wider outbreak of the virus within the United States will likely occur soon. Naturally, mosquito containment has become a top priority for health officials in both infected areas and those likely to be impacted by the virus. The standard list of mosquito control protocols includes pesticide repellents, mosquito nets, eliminating stagnant open water sources, and long-sleeved clothing to limit skin exposure. In addition to these, health authorities are considering a number of new strategies based on genetic engineering technologies.

 

One such technique employs the concept of gene drive, the fact that some “selfish” gene alleles can segregate into gametes at frequencies higher than the expected Mendelian ratios. In this scenario, gene drive can be exploited to spread a disease resistance gene quickly throughout a population of mosquitoes. Recently, a team at the University of California tested this idea by using CRISPR technology to engineer the mosquito Anopheles stephensi with a malarial resistance gene drive. After integration of the resistance gene cassette and DNA targeting with CRISPR, this gene was successfully copied onto the homologous chromosome with high efficiency, thus ensuring that close to 100% of its offspring will bear resistance. Possibly, similar techniques could be exploited to engineer Zika resistance in Aedes mosquitoes.

 

In contrast to engineering disease resistance, an alternative defense strategy is to simply reduce the population of a specific mosquito species, in the case of a Zika outbreak, Aedes aegypti. The WHO has recently approved a GM mosquito which, after breeding, produces offspring that die before reaching adulthood. This technique can dramatically reduce an insect population when applied in strategic locations. The British biotech firm Oxitech has also developed its own strain of sterile Aedes aegypti males. In laboratory testing, these GM mosquitoes compete effectively with wild males for female breeding partners. The short-term goal is receiving approval to test these sterile males in the wild; ultimately, a targeted release of these mosquitoes will reduce the Aedes aegypti population in Zika hot spots without affecting other species.

 

In parallel to mosquito engineering, other work has focused on studying the mechanisms underlying Zika’s dramatic affects on the brain. To study the process of Zika infection in vitro, scientists at Johns Hopkins cultured 3-D printed brain organoids and demonstrated that the virus preferentially infects neural stem cells, resulting in reduced cortical thickness owing to the loss of differentiated neurons. This neural cell death may explain the frequent microcephaly observed in fetuses carried by infected mothers.

 

Much like the recent outbreak of Ebola in several African countries, this event helps underscores the importance of basic research. A recent New York Times article drew attention to this fact by highlighting the need for more complete genome sequences of the mosquito species that carry Zika. With a complete genome sequence at hand, researchers might be able to piece together information in answering questions such as: why are some Aedes mosquitoes vectors for Zika and others aren’t? Species differences in genome sequence may provide some answers. Nevertheless, greater knowledge of the mosquito’s biology will yield more options for human intervention. This is an excellent case study in how ‘basic’ and ‘translational’ research projects can co-evolve in special situations.