Going Beyond the Bench for Good: Alternate Careers for Science PhDs

For various reasons, ranging from imposter syndrome to burnout, I’ve thought a lot (but mostly in vague terms) about “alternative careers.” During my PhD third year slump I was even convinced, much to the chagrin of my advisor, I was going to join the Peace Corp. But a few months later, research picked up, leading to my first publication. I again felt the thrill of discovery and decided to pursue the next rung in the academic ladder: a postdoc.

Still, nowadays drive and interest in research are often not enough as less than 20% of PhD graduates are in tenure-track positions five years later. And so it is important to keep other careers in mind. For me at least, the only apparent “alternatives” were teaching or industry. But after years of attending discussion panels, talking to former colleagues, and delving into (somewhat unhelpful) books, such as “Alternative Careers in Science: Leaving the Ivory Tower” I realized there are a lot more options available. Therefore I thought it would be valuable to share what I learned and hopefully get other suggestions, anecdotes, or comments in return. The sections presented below include Science Policy, Teaching on various levels, Consulting, Writing and Communication, etc.

Science Policy

The realm of public policy that involves science, including funding of science and research, promoting technological innovation, monitoring environmental issues, and of course health care policy. As someone with no experience in politics I didn't know what a career in science policy looks like. Luckily, there is an article in ASBMB today titled “What Is Science Policy?” The author describes the field thus: “Science policy experts thus serve as the bridge between researchers and the public, using their talents to find ways to translate esoteric, often highly technical scientific issues into something that can be sold as good policy.” Policymakers can work either for legislators or for scientific societies.

Paths for entry:

There is a wealth of fellowships, offered by different organizations. Most are through government agencies and most offer stipends. Many will want writing samples to demonstrate that you can explain scientific concepts to the general public. One possibility is to volunteer writing for department or university newsletters.

OSTP Internship Program: 3-month unpaid internship with Office of Science and Technology Policy, which advises the President on the effects of these issues on domestic and international affairs.

Phoebe S. Leboy Public Policy Fellowship:  2-year paid fellowship with the Association for Women in Science in D.C. Work includes analyzing policy issues related to gender and science, working with advocacy agencies, preparing advocacy documents, and attending conferences.

American Society for Biochemistry and Molecular Biology: 1-2-year paid fellowship for recent PhD graduates with public affairs office of ASBMB.

FDA ORISE Fellowship: Paid (no benefits), gives recent graduates “opportunities to participate in project-specific FDA research and developmental activities.” This is rather vague but from a former colleague is in the program I learned that the duties and experience is very specific to position so that some fellows do lab work while others do not. Non-lab work includes reading scientific papers, data organizing and analysis.

FDA Commissioner’sFellowship Program: receive regulatory science training and work on science, regulatory, and policy issues. Specifically for those with a PhD.

NIH/NHGRI Geneticsand Public Policy Fellowship: "Designed as a bridge for genetics professionals wishing to transition to a policy career.” 16 month, paid with benefits with 3 rotations: NIH, Legislative Branch, nonprofit science advocacy sector.

Christine MirzayanScience & Technology Policy Graduate Fellowship Program: 12-week ($8,500 stipend) at National Academy of Sciences working with a mentor to learn about science and technology policy through an immersive (ie intense) experience.

AAAS Science &Technology Policy Fellowship: 1-year. “Fellows engage their knowledge and analytical skills while learning first-hand about policymaking and implementation at the federal level.”

Science Writing/Communication

Science writer:

A science writer can write for either the general public in a newspaper or magazine, distilling the science, or to other scientists, for example, writing the “Perspectives” column in peer-reviewed science journals. Clearly journalism as a whole has come on hard times and so not surprisingly, most jobs are freelance. Though salaried positions are to be found. Part of the job of a science writer is to decide which discoveries are important for the public to know about.

Point of entry: There are Master’s programs for science writing and communication as well as some fellowships, including the AAAS Mass Media internship. A good resource for those interested is the National Association of Science Writers.

Medical writing:

This broad category includes writing reviews or practice guidelines for medical societies and writing the manuscript for publishing results from clinical trials. The former means communicating and coordinating with the doctor’s actual conducting the studies. Often times, this writing is contracted out to companies by the hospital. Finally, medical writing can include writing the labels that go on drugs.

Editor at a Scientific Journal:

I saw job postings for assistant editors open to recent PhD graduates, but postdoctoral experience seemed to be preferred. Generally, strong communication and interpersonal skills, ability to meet deadlines, and multitasking is required. Some positions include travelling to conferences to promote the journal. Here is a good anecdote of someone who transitioned from apostdoc to editor. 

Freelance Editor:

Edit content, form, style, and language for research groups submitting their papers for peer-reviewed publication. Have to check for both language and scientific mistakes (figures match up with text). The speaker on the panel said she gets a lot of non-English-speaking clients. She said that in order to break into this field as a freelancer, she volunteered to edit many papers for free and then depended on word of mouth.

Consulting

Okay, if someone has a concrete description of this job, other than strategic problem solving for clients, please tell me. I became aware of this job only because of recruiters coming to school from various consulting firms, including McKinsey and the Boston Consulting Group. Another popular one is Booz-Allen & Hamilton. From what I heard you are generally assigned a specific project and may have more than one project at a time. Often travel is required, but there is some job flexibility. Oh yeah, and the possibility for a pretty good paycheck. Additionally consultants can work for themselves or with a firm and may or may not be permanent employees. I had a pretty good idea this wasn’t for me, but for more information, check out http://biocareers.com/resource/getting-started-consulting.

Marketing

This involves marketing products from different scientific companies like Eppendorf, to laboratories. No offense but this job is a bit too schmoozey for me. But I met someone at a discussion panel who seemed to genuinely enjoy her job. She said it involves travelling to different universities companies and talking to people (the amount of travel depends on whether you live in a city or more rural) and learn about new products than can help the client. She enjoyed gaining sales experience. The hours seemed pretty good with only a bit of work required from home to give clients a quote or set up an account.

Tech Transfer

When a lab in a university develops a technology, such as a drug or vaccine, they first check with the university’s technology transfer agency to assess the possibility for a copyright, patent, or trademark. The job requires basic science knowledge as well as patent law, business, and marketing skills because the transfer specialist has to determine the potential for intellectual development, identify companies to approach, and even pitch the product and negotiate contracts. The job is fairly varied from day to day and was described as “moderately stressful.”

Teaching

At the college-level:

If you only want to teach without maintaining your own lab at the college-level, you are most likely looking at either a full-time position at a liberal arts school or community college (which usually don’t conduct research) or a part-time/adjunct position. Many science courses have a laboratory component, which you as the instructor would be responsible for. Additionally certain universities may want faculty to run a small lab to support undergraduate research projects.

What to expect when applying: The university/college will most likely request a teaching statement and possibly a teaching portfolio. It seems that many colleges/universities hiring full-time faculty require 1-2 years of teaching experience preferably at a similar institutional level (i.e. community college if you’re applying to a community college). I was told that postdoctoral experience is preferred, even for teaching-only positions. There are increasingly more “teaching postdocs” available and many universities have either classes or certification programs to expose scientists to pedagogy.

Resources: http://cft.vanderbilt.edu/guides-sub-pages/teaching-statements/

Where to look: Sites such as Chronicle of Higher Education, Higher Ed Jobs, Inside Higher Jobs

At the high school level:

Admittedly, I don’t know too much about this. Most states will require a certification or licensing, an exam to test competency, background check (obviously), and possibly “student teaching” experience. It appears that the bureaucracy is a lot less for private school, but so is the pay. I came upon an interesting looking online teaching certification program called TeachNow.

Nonprofit/Science Outreach

Society for Science and the Public: – publishes Science News and organizes education programs such as the Intel International Science and Engineering Fair (of which I am a 2002 alumnus ;)) and the Broadcom MASTERS. They have internships and jobs as science writers and editors.

One panel member was a science historian for the Chemical Heritage Foundation in Philadelphia. Her job entailed conducting oral history interviews with scientists as well as contributing to the foundation blog, writing a monthly feature for the foundation newsletter. The CHF also does outreach programs to get women in chemistry.

Other nonprofit organizations:

Alfred P. Sloan Foundation

AAAS (see science communication and policy sections)

Patent Law

Work for a law firm, which is hired by drug companies to do searches for claims on patents and litigation support. Often, the firm will pay for you to go to law school, although the panel speaker I heard did not have or want to get a law degree.

Point of entry: Panel member emailed law firms to find position.

The Skinny on Sweeteners

As someone who became weight-conscious just as Splenda® was coming on the market with the slogan, "it takes like sugar because it is made with sugar," I ate up the promise of no guilt sodas and sweets, literally. And I have been a loyal customer ever since, always carrying a few packets, in various forms of disintegration, in my purse, just in case. So needless to say I approached the recent warnings on the potential harmful side effects of artificial sweeteners with much interest, and I should add, skepticism. Previous studies have shown mixed results and often were conducted with very small sample sizes. That said I found the study published in Nature last week, “Artificial Sweeteners induce glucose intolerance by altering gut microbiota”, intriguing, albeit not without it’s drawbacks (Suez et al., 2014).

First off, the authors look at the effects of three common non-caloric artificial sweeteners (NACs) on glucose tolerance in mice. Glucose tolerance is a test that measures clearance of glucose from the bloodstream, usually two hours after ingesting glucose. Elevated levels are an indicator for insulin resistance and pre-diabetes. Sucralose (in Splenda®), aspartame (in Equal®), and saccharin (in Sweet’N Low) all led to higher glucose levels in mice, although by the final two hour time-point, the difference to the control group became less significant. For the rest of the studies, they focus on saccharin and show that there is still a significant effect on glucose levels when lower doses, corresponding to the FDA’s maximum acceptable daily intake (ADI) dose are given for five weeks.

In recent years, the importance of commensal bacteria living in the gut (the gut microbiota) in immunity and metabolism has become appreciated. Therefore the scientists wanted to determine if gut microflora had an impact on the mice's response to saccharin. Remarkably, saccharin ingestion no longer led to glucose intolerance when broad-spectrum antibiotics were given to mice concurrently with saccharin for four weeks. The author’s measured the composition of the types of bacteria present in the stool of the mice fed both diets and discovered that the composition of the microbiome was distinctly different from the control mice and that it had changed considerably from before the mice were given saccharin.

To determine a causal relationship, the scientists took bacteria-containing stool from saccharin-fed mice and transplanted them to the control mice, which then exhibited glucose intolerance when measured six days later. Stool from control mice cultured in vitro (in culture, outside the body) and then transplanted to non-sweetener-fed mice also had glucose tolerance impairment, providing strong evidence that saccharin changes the type of bacteria present in the gut, which in turn negatively effects the metabolism in mice.

But what about humans? Here they look at 381 non-diabetic people and using questionnaires about food intake, including sweetener use, they find a positive correlation between long-term sweetener use and several parameters of metabolic impairment, including glucose intolerance tests. In the final, and perhaps most startling part of the study, seven individuals with no history of sweetener use were given the FDA ADI dose of saccharin for six days, glucose tolerance was measured, and stool samples were taken for analysis of the gut microflora. Four out of the seven showed impaired glucose tolerance. Interestingly these “responders'” microbiome was very different from the “non-responders'” (those whose glucose levels did not change significantly after being given saccharin) and the microbiome of the responders changed after treatment while the non-responders did not. Finally, stool from responders was able to induce glucose intolerance when transplanted to mice while non-responders’ did not.

These final results are very intriguing but the sample size is so small as to make it hard to make definitive conclusions. In case you are curious as to whether the doses given (360 mg) were comparable to what an average user may ingest, 360 mg of saccharin would be the equivalent of 10 packets of SweetN’ Low® (so maybe 5 cups of coffee with 2 packets each). Most sodas stopped using saccharin awhile ago, but Tab soda, where available, contains 64 mg of saccharin, so 5 to 6-12 oz. cans of Tab everyday are needed to reach the levels in the study. 

Still, the study is important and deserves its publication in the prestigious journal, Nature. It is not the first study to discover a change in microflora with sweeteners. It appears, that Splenda® leads to changes in gut microbiota in mice as well (Mohamed et al., 2008) and led to increased glucose levels in the blood and humans (Pepino et al., 2013), although only seventeen people were tested in the latter study. Of course, it makes me interested to know if I am a responder or not and if we can eventually take stool samples and predict whether a persons’ microbiome will be negatively affected by sweeteners? While I would not advocate for others to change their sweetening habits based on this study, I would strongly suggest for similar studies with larger population sizes and perhaps lower, more normal doses, over longer periods of time. 

References:

Mohamed B., et al. (2008). Splenda Alters Gut Microflora and Increases Intestinal P-Glycoprotein and Cytochrome P-450 in Male Rats. J. Tox & Env Health, 71. doi: 10.1080/15287390802328630.

Pepino M. Y., et al. (2013). Sucraolse affects glycemic and hormonal response to an oral glucose load. Diabetes Care. doi: 10.2337/dc12-2221.

Suez, J., et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. doi:10.1038/nature13793

How I get through some days in lab...

So I love listening to public radio while in the lab. It's a problem because it can be hard to concentrate on both science and Terry Gross' probing questions, but luckily I am pretty good at "multi-tasking." Podcasts are especially helpful while doing those tedious lab tasks such as minipreps, transformations, and well, everything (except maybe analyzing the results and planning future experiments).

The newest podcast I am addicted to is Stuff You Missed in History Class. The link is for a science-related cast from June titled "Caroline Herschel: Astronomy's Cinderella." She broke through many barriers for women in science in the late 1700s in equal measures through her relationship with her astronomer brother and her persistence. She identified and catalogued stars, comets, and nebulae.

Dorothy Hodgkin: From Nobel Laureate to Google Doodle

http://www.google.com/doodles/dorothy-hodgkins-104th-birthday

The first time I heard of Dorothy Hodgkin was last May when Google featured her model of Penicillin as its doodle. Side note: I actually didn't see it myself, but was lucky enough to have a mother-in-law who was interested in my science and pointed it out to me. Having completed my dissertation in X-ray crystallography, I was surprised to not have heard of her before: the third woman to win the Nobel Prize in Chemistry for “her determinations by X-ray techniques of the structures of important biochemical substances (1).” The two other women were of course Marie Curie, and unbeknownst to me, her daughter, Irène Joliot-Curie. Dorothy Hodgkin determined the X-ray structures for important biomolecules, such as penicillin and Vitamin B12, as well as making her mark on protein crystallography. Her structure of Vitamin B12 allowed for the synthesis of the vitamin to treat megaloblastic anemia. I’ve written a separate post describing the field of X-ray crystallography in more detail here.

 Structure of Vitamin B12, one of the most complex structures that  had been determined by 

X-ray Crystallography at the time.  Image courtesy of chemicalheritage.org

It was apparent from my readings into her life that Dorothy Hodgkin is an example of the type of scientist I always hoped to be: committed, passionate, and steadfast about her work and its implications, well rounded and diverse in her interests, humble, yet confident in what she wanted in her life from an early age. Of course, sexism is not hard to find in her story. The headlines when she won the Nobel Prize in 1964 was "British woman wins Nobel Prize – £18,750 prize to mother of three." in the Telegraph and "Oxford housewife wins Nobel" in The Daily Mail. But she seemed to rise above it all.

Her father taught and worked in archaeology in Egypt, the Sudan, and Jerusalem and Dorothy would visit at different times in her life (2). She carried a love of Africa throughout her life, later making many trips to Ghana while her husband worked at the University of Ghana, and even for a time as advisor to the Ghanaian president (2,4). Eventually, her daughter would teach in Zambia (2).

Dorothy’s life is rife with the stuff of good dramas. According to a 1998 biography, her very influentional advisor, J.D. Bernal and she were lovers on and off for years, even after she married (3). The politics of this advisor, as well as her husband’s were of a communist persuasion and she was banned from travelling to the U.S. without a CIA waiver (4). It is unclear if she held the same political views but after being refused entry to the U.S. to attend a conference organized by Linus Pauling, she travelled to the Soviet Union, attempting to set up scientific collaborations. She also visited China many times throughout her career and had many collaborations with Chinese and Indian scientists. She campaigned for inclusion of countries into the International Union of Crystallography such as China and the Soviet Union, who were banned for political reasons (4).

Dorothy believed it was the responsibility of scientists to help make the world a better place. She was president of the Pugwash council from the mid 1970s to late 1980s (4). Never heard of the Pugwash conferences? Neither had I. Pugwash is an international organization established in the years following WWII, bringing together scholars with the goal towards international conflict resolution and nuclear and chemical weapon disarmament.

Dorothy Hodgkin, image courtesy of chemicalheritage.org

What drew me to her, more than her politics though was her dedication to solving a particular problem. She studied one protein, insulin for more than 35 years, eventually solving the structure. In her Nobel Lecture she recounts a sentence from the W.H. Braggs book “Concerning the Nature of Things” which peaked her interest in the field as a teenager, “”Broadly speaking, the discovery of X-rays has increased the keenness of our vision over ten thousand times and we can now ‘see’ the individual atoms and molecules.”” A few sentences later she writes, “The process of 'seeing' with X-rays was clearly more difficult to apply to such systems than my early reading of Bragg had suggested; it was with some hesitation that I began my first piece of research work with H. M. Powell…(5).” Four years after giving this lecture she finally determined the structure. When she originally set out in the 1930s, the technology and methodology was not advanced enough to study proteins. She continued to.. Her structure contributed to the knowledge of receptor/hormone binding and allowed for reliable synthesis of the hormone as a treatment for diabetes. 

This part of her story resonated with me as I remember seeing the beautiful pictures of protein structures in late bachelor studies and trying to wrap my mind around how one came to these pictures. Indeed, I would discover it was more complex than even I imagined. And I was lucky to benefit from all the amazing advances that semi-automate the steps along the way from setting up hundreds of crystal conditions (or in my case, thousands) to shooting the crystals with X-rays in California while sitting in my house in Baltimore to solving the structure using information gained by other crystallographers on similar proteins. Even with these advances, it took three and a half years to determine the structure of my one and only protein, Plasmodium falciparum Atg8.

It was with some sadness that I left the crystallography world behind, with its helpful and always willing to commiserate, yet highly critical, compatriots. My experiences make me appreciate all the more the contributions that Dorothy made in the then male-dominated and inchoate field of biomolecular and protein X-ray crystallography.

References:

1. (2014). Dorothy Crowfoot Hodgkin - Facts. Nobelprize.org. Nobel Media.

2. (2014). Dorothy Crowfoot Hodgkin – Biography. Nobelprize.org. Nobel Media AB 2014. Retrieved August 24, 2014. Retrieved from http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1964/hodgkin-bio.html.

3. Ferry, Georgina (1998). Dorothy Hodgkin: A Life. London: Granta Books.

4. Howard, J.A.K. (2003). Dorothy Hodgkin and her contributions to biochemistry. Nat Rev MCB. 4, 891-896.

5. Hodgkin D.C. (1964). The X-ray Analysis of complicated molecules. Nobel Lectures. Chemistry 1963-1970, Elsevier Publishing Company, Amsterdam, 1972.

A quick introduction into protein X-ray crystallography:

What information do we get from X-ray crystallography?

Proteins, which are the machines inside our cells that use energy to do countless tasks, such as copy our DNA for the next cell, cause our muscles to contract, bind hormones, allow our neurons to release hormones and neurotransmitters. It is vastly helpful to understand what proteins look like, their 3-dimensional structure, to understand how they work. For example, take the protein, DNA helicase. In order for our genome to be passed on to newly-divided cells or our progeny (in the form of sperm and egg cells), it must be copied. In order to be copied, it must be temporarily pulled apart from its more stable double-stranded form, to a single stranded-form where the information is accessible. DNA helicase is a motor that uses energy from ATP to unwind the DNA. In the image below, you can see that the structure of one molecule of the protein, which alone doesn’t really explain its function. But the protein binds five other identical helicase molecules to form a donut-shape, which encircles one strand of the DNA. The motor then drives the helicase forward, pulling the two strands apart by shear force.

 

 (PDB code: 2R5U) (http://www.pdb.org/pdb/explore/explore.do?structureId=2R5U)

This crystal structure is specifically of the helicase protein from the tuberculosis bacteria. Knowing the structure allows scientists to design drugs that bind the protein in the bacteria, but not in humans, and to prevent the bacteria from replicating.

How do we get this information?

Proteins are extremely small, too small to see with the human eye and the structure is too small to see with a microscope. But if we can get the protein to crystallize, forming a regularly repeating structure that is much bigger than the single protein alone, we amplify the signal-to-noise ratio. X-rays are then shot at the crystal. When the X-rays hit the atoms that make up the protein, they are diffracted, that is, the direction and intensity change. The pattern of diffraction provides information about the position of the atoms in the protein and the diffraction pattern is captured by a special camera device behind the protein. Of course, back when Dorothy Hodgkin was solving the structures of penicillin and Vitamin B12, there was no camera, the diffraction pattern was recorded on X-ray film. Using mathematical formulas, we can then backtrack to the structure, but there is a big caveat; some information, the phases, are missing from the diffraction pattern. There are several ways, which I won’t go into here, for crystallographers to get the missing information and solve the structure.

Dorothy Hodgkin contributed to the methods available to get this missing information and solve the phase problem. This included using selenium derivatives and using microorganisms to incorporate the selenium into the protein.

The what and why of the Ebola virus disease

 Electron micrograph of Ebola virus (Cynthia Goldsmith, CDC (wikimedia commons)

With the death toll surpassing one thousand, this is the largest Ebola outbreak since its emergence in 1976. The outbreak is unusual in its occurrence on the west coast of Africa rather than central and also in its spread to urban areas. The outbreak has received much news coverage in recent weeks as the death toll rises and two Americans infected were flown home to receive “experimental therapy.” Why does the outbreak capture the international attention so much more than diseases such as malaria, which kills three times that number…in one day? Perhaps one reason is that malaria is perceived as a chronic condition in developing countries, with eradication a far-fetched goal. The horrific effects of Ebola, hemorrhagic fever, internal bleeding and death resulting from multiple organ failure are probably even more of a contributor. This, combined with a mortality rate of up to 90% (though the numbers are closer to 60% in the current outbreak), makes for a terrifying disease. With the announcement by the WHO this week that experimental drugs can be used in Africa, it seemed like a good time to write a post about the biology behind the Ebola disease and how these much-discussed experimental drugs work. I apologize in advance if this information seems basic to readers in the scientific field, especially virologists, but this post is aimed at those less familiar with science.

The pathogen that causes Ebola is a virus. Viruses are different from bonafide living organisms in that they lack cellular structure and cannot make their own proteins. Proteins are the workhorses of the cell, molecular machines that replicate the genome, allow cells to divide, secrete, move, etc. But viruses are just genetic material, either RNA or DNA, enclosed in a protein coat and possibly a lipid envelope (depending on the type of virus). In order to make more of themselves, the virus must invade cells, be it cells of bacteria, plants, or mammals, and hijack the host machinery. The Ebola virus is a single-stranded negative sense RNA virus. This refers to what has to happen inside the host cell in order to replicate. Its genome is encoded in RNA, which, although very similar to DNA (used by most organisms to encode their genome), is chemically less stable than DNA. The virus has a helical protein coat that protects its genome, giving it a striking long filamentous appearance.

Journey of the Ebola virus:
The virus can spread to a new person when blood or body secretions containing the virus come in contact with mucus membranes or broken skin. A glycoprotein (made of a chain of amino acids and sugar) forms spikes on the virus surface and attach to the host cells. The viral proteins bind receptors on the host cell and trick the host cell into engulfing the virus, bringing it inside the cell (Saeed et al., 2010). The virus then needs to make a version of its genome that the cell can read like a blueprint to make more RNA genome, as well as the structural elements of the virus. Luckily for the virus, it has brought a protein, made during its previous infection to convert the genome into a proper blueprint. The newly copied and packaged viruses then must get out of the cell and invade new ones. The Ebola virus “buds” from the host cell, enclosing itself in lipids from the plasma membrane of the host cell, which is the barrier that separates cells from their environment. One protein in particular on the virus envelope is central to this step and is therefore being investigated as a potential drug target (Jasenosky et al., 2001, Timmons et al., 2001). However this is not what is in the ZMapp drug given to three Ebola patients.

Why is Ebola so deadly?
While some viruses infect only certain types of cells, the Ebola virus spreads through the blood system to infect cells in many organs. Patients often suffer liver, kidney, and other organ failure. A major contributor of the mortality of the disease is “immune paralysis” where patients are unable to mount a defense. This is because many of the proteins the virus makes are specialized to interfere with our defense systems allowing the pathogen to wreak havoc unchecked (Lubaki et al., 2013). For example, while our immune system is designed to sense viral RNA (double stranded RNA), a protein made by the Ebola virus covers and hides the RNA from the host. And any amount of interferon signaling activation that is achieved is inhibited later on by the same and other viral proteins (Leung et al., 2010). Additionally one of the first cells infected by the virus are macrophages, immune cells required early on to recruit other immune cells.  This both prevents them from doing their job and causes them to secrete substances that leads to the cell death of other immune cells and makes capillaries leaky, causing internal bleeding (Geisbert et al, 2003).

What’s in this experimental drug?
When infected by bacteria or viruses, our immune systems produce antibodies, “Y”-shaped proteins that bind a protein on the foreign invader similarly to a lock and key mechanism, using the two tips of the “Y”. This neutralizes the pathogen and recruits other parts of the immune system. Therefore antibodies against Ebola virus injected into a patient could help fight the infection.

But where can we get these antibodies?
Mice similarly produce antibodies so scientists at Mapp Biopharmaceutical injected mice with the virus and harvested the antibodies the mice produced. After identifying the antibody reactive against Ebola, they modified the genetic blueprint encoding the antibody so it looked more human-like. This is to prevent an immune reaction in humans, in which the immune system would see the injected antibody as a foreign invader rather than a helping hand.

How to make large amounts of this antibody? 
Since all organisms use the same genetic code, scientists can make all kinds of cells produce the protein of their choice. In graduate school, I made E. coli bacteria produce proteins from the malaria parasite so that I could study the protein more easily (hence my comment about the deadliness of malaria in the introduction). However since bacteria aren’t very good at making complex antibodies, mammalian cell lines are often used instead. Mapp Biopharmaceutical uses tobacco plants because production is faster and cheaper. The DNA is inserted into the plant cells and the plant’s machinery makes the recombinant protein, which is then harvested. ZMapp, the serum that was used on the two Americans, is a combination of antibodies made in this way. It is important to keep in mind that although the two American patients appear to be responding positively to ZMapp, it is impossible to determine from this that the drug works. The only way to determine the effectiveness of a drug is through clinical trials in which a control group receives a placebo. However with both the ethical questions of testing drugs in developing countries and the extremely short supply of serum, clinical trials are unlikely to occur in the near future.

References:
Geisbert, T., et al. (2003). Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques. Am J Pathol. 163, 2347-2370.

Feldmann H., et al. (2001). Biosynthesis and role of filoviral glycoproteins. J Gen Virol. 82, 2839-48.

Jasenosky, L. D., Neumann, G., Lukashevich, I., and Kawaoka, Y. (2001). Ebola virus VP40-induced particle formation and association with the lipid bilayer. J Virol. 75, 5205–5214.

Lubaki, N.M., et al. (2013). The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results from the Cooperative Effect of at Least Two Viral Domains. J Virol. 87, 12506.

Leung, D.W., et al. (2010). Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nat Struct and Mol Biol. 17, 165–172.

Timmins, J., Scianimanico, S., Schoehn, G., and Weissenhorn, W. (2001). Vesicular release of ebola virus matrix protein VP40. Virol. 283, 1–6.

Saeed, M. F., et al. (2010). Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes. Plos Path. 6, 1-15.

Wahl-Jensen, V., et al. (2005). Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function. J Virol. 79, 10442-10450.