Scientific breakthrough of the month (if not year): Paralyzed man walks again after cell transplantation

Last month saw a major medical breakthrough: a man paralyzed from the chest down is now able to walk with a frame after transplantation of specialized cells from the nasal cavity into the spinal cord. Darek Fidyka, 38, became paraplegic after being stabbed in the back multiple times 2010. This resulted in almost complete severing of the spinal cord the injury. In 2012, team of researchers from Poland and the UK transplanted cells from the olfactory bulb into the spinal cord of the man at the site of damage. Roughly two years after the procedure, the patient is able to walk with assistance and has regained feeling in his lower body. The results were published in Cell Transplantation in October (1). 

The procedure takes advantage of the fact that olfactory nerves, responsible for our ability to smell, continue to regenerate in adulthood. Nerves from the nose epithelium travel to the olfactory bulb, located in the base of the brain, which further transmits the smell signal to other parts of the brain. Specialized cells called olfactory ensheathing cells (OECs) surround the nerve fibers and support cellular regeneration.

Researchers hypothesized that these cells could help regenerate other nerve fibers, such as those in the spinal cord. Transplantation of OECs to damaged spinal cords in mice and rats led to improvement; however, the procedure had never been done in humans before (2). To harvest the OECs, part of the patient’s skull was temporarily removed. The olfactory bulb was then removed from one side and cultured in a petri dish. Other cells, such as blood vessels, were removed and the OECs and their accompanying olfactory nerve fibroblasts were allowed to grow for 12 days. The cells were then injected into the spinal cord stumps and along the rim of the residual cord with a tiny needle. Nerves from the patient’ leg were grafted to bridge the 8 mm gap between the spinal cord break.

The first signs of improvement occurred around 4 months after the transplant with restoration of some sensation in parts of the body and voluntary muscle contractions at around 5 months. But the road to recovery was still long with pivotal progress occurring 10 months after the procedure when Fidyka was able to flex muscles in the legs and muscle mass increased.  However, most of the improvement has been to the left side of his body. As expected, Fidyka initially lost sense of smell on the side where the olfactory bulb was removed, but surprisingly, he later regained some sense of smell.

It is unlikely that Fidyka’s ability to walk was due to spontaneous recovery as several studies have concluded that spontaneous recovery in paraplegic patients of this type most likely occurs within the first six months. In contrast Fidyka showed no sign of improvement up to the procedure, 21 months after injury. He had undergone extensive rehabilitation prior to and after the transplantation.

Fidyka’s drastic improvement indicates the spinal cord was able, with the help of OECs and the nerve graft, to repair itself. However researchers stress that this is only one patient and needs to be repeated before drawing too many conclusions. Additionally, the spinal cord injury was relatively new and the cord was not completely severed. Still the study highlights the potential of OECs as a therapy in spinal cord injuries as well as possibly, in neurodegenerative disorders. 

References:

1. Tabakow, P., et al. (2014). Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. Online

2. Deumens, R.. et al. (2006). Olfactory ensheathing cells, olfactory nerve fibroblasts and biomatrices to promote long-distance axon regrowth and functional recovery in the dorsally hemisected adult rat spinal cord. Exp Neurol (1): 89-103.
 

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