### Archives For October 2012

A couple weeks ago, Felix Baumgartner set the record for the longest free fall, previously held by Captain Joseph Kittinger. To be more specific, Baumgartner dove from 39 kilometers in 2012, and Kittinger dove from 31 kilometers in 1960. However, Baumgartner traveled faster, with his total dive taking 17 seconds less than Kittinger’s. This was the true feat, as he reached 1,342 kilometers per hour, thus breaking the sound barrier.

At 39 kilometers, how high up was Baumgartner? This is 8% short of a full marathon, the distance of 4.4 Mount Everests stacked atop one another, and 3.6 times the greatest depth of the ocean. At this height, the temperature is only -25.6 C, the pressure is only 1/3 of that on the ground, and the effect of gravity was still 98-99% of what it would be at sea level. His maximum speed of 1.1 Mach (the speed of sound in dry air at 15 C and 1 atm) was just 13% short of the maximum speed of the X-1 rocket plane. In other words, he was moving very fast from an extreme height.

If you want to consider how this might affect a human, you must consider not speed, but acceleration. With the Stratos jump, it took Baumgartner 42 seconds to reach his terminal velocity. This is pretty quick. How did he do it? When in free-fall, we can consider two forces, drag and gravity. I noted above that the effects of gravity were reduced, but not by much, at this elevation (to 9.7 meters per second-squared, to be specific). The force of drag acting on a body is dependent upon its velocity. So, as you fall and gain speed, the effects of drag become greater. Eventually, drag force becomes great enough such that you cannot accelerate any further from gravity, and you reach terminal velocity. This is usually 25 m/s for most objects. However, Baumgartner was in the stratosphere. The air pressure, as I mentioned above, was only 0.33 that of what is at sea level. With such low air density, the effects of drag are reduced. The force of acceleration, relatively unchanged, provides a strong downward force (toward the Earth). This leads to a very high terminal velocity, one that can break the sound barrier. (I should note that the speed of sound is reduced at high elevation because sound propagation is dependent upon the density of the medium through which the wave travels.)

What does this have to do with acceleration, then? We know his speed was significant, and we know he did it quickly. According to the argument above, the only real force leading to acceleration is gravity, and we have an upper limit of 9.7-9.8 m/s^2. The numbers reported agree with this, with an average acceleration of about 8.8 m/s^2. Is this fast enough to hurt a human? Again, what matters is accelerationnot speed. This discussion started in WWI, where pilots reported vision problems with high-acceleration maneuvers. Today, we see it ranging from the design of rockets by NASA to safety reports in four-door sedans. If we look back at other human endeavors, we see a story of high acceleration. The now-retired shuttle missions accelerated astronauts to three times the force of gravity. The Apollo missions entered the atmosphere at six times the force of gravity upon their return home. However, the highest reported cases were with the Daisy Decelerator in the 1970s. Major Beeding was placed in this capsule, and he was decelerated at 83-times the force of gravity for approximately 0.04 seconds. He survived, emerging with a short period of shock and a bruised back. While I wouldn’t claim that most humans could survive such an extreme scenario, this demonstrates the importance of acceleration over total speed. With Baumgartner traveling at <1g (less than one times the force of gravity), this provided little danger.

Whether or not this provided a danger to the diver, it was an exciting watch. Whether or not it advanced our knowledge of the stratosphere, it gave me a fun topic for this blog post.

As promised before, I plan to write on topics related to my experience in medical school, graduate school, and the combination of the two. For those who do not know, I am a student in an MD-PhD program (thus the “MudPhud” in the title of the blog). The classic paradigm is one that follows a 2-4-2 model of training. Our particular program follows the following pattern:

• 2 years of medical school – These are the preclinical years, where we study biochemistry, histology, pathology, physiology, pharmacology, and related topics. It is mostly lecture-based, though our school utilizes a problem based learning (PBL) model. A few graduate school courses are taken in parallel with medical school.
• 3.5-4.5 years of graduate school – We then transition to graduate school, where a few courses are taken in the first year of graduate school (third year in the program). After rotating in multiple labs during the previous years, we settle into a lab and perform research for the following years. This ends with the defense of a doctoral dissertation.
• 1.5 years of medical school – These are the clinical years, where students practice on the wards in each of the required fields. This portion of training culminates in graduation from the medical school and thus the MD-PhD program.
• After the program – Students take multiple paths, ranging from medical residency to a postdoctoral fellowship to work in industry. Most will go on to residency.

The challenge in the transition from medical school to graduate school is not an easy one. In medical school, one must acquire large quantities of data and share this knowledge at regular intervals (usually on written exams). One could consider it like a very fast treadmill where you do not have access to the controls. The treadmill will continue to push you, but you may feel challenged to keep up. Or you might not feel this challenge. To be honest, I did not find this to be too fast, but the challenge for me was the lack of control over my schedule, from an emotional standpoint. During this time, you build a rapport with a large group of classmates who will later become colleagues. The shared experience of medical school creates solidarity among this group.

In graduate school, things change. You are now on your own, in a place where you are now at the bottom rung once again. It is exciting on one hand, because you can now choose what to study and how to direct your education. On the other hand, you may feel lost. As opposed to a treadmill, this is more like jogging through a forest, where vision is limited. You can take breaks to reorient yourself, and you can move at your own pace. However, it is difficult to know whether you are making progress, how fast you should be moving, or whether you are completely lost. Your friends in medical school are now moving on, and you no longer share the rapport you previously had with them. This creates a distance, and it is often emotionally trying.

For as challenging as the graduate school transition might be, the benefits outweigh the drawbacks. You are now able to study what truly fascinates you. You have control over your schedule, and you determine your own pace. You have access to a vast array of resources, and you can take on additional projects outside of your program. For example, I found myself volunteering with mentorship programs, science fairs, and even with a community clinic. The challenges you face in graduate school make each success far more rewarding than if they were easy. A simple rotation or a year-long research project cannot create the same level of suspense, mostly due to their limited timelines and more structured projects. Failure begets learning. Success begets inspiration.

The recent results from the trial of Lance Armstrong compels me to write about doping in some fashion. Many articles have been written on the topic lately, so I will focus instead on a different topic. Doping is particularly widespread, and it has been the focus of numerous debates. What else can be said about the issue? I will bring to light another approach, an historical account of doping. To do so, let’s flash back to the 1904 Olympics.

Thomas Hicks was a marathon runner from the United Kingdom but representing the United States at the Summer Olympics in St. Louis. He crossed the finish line second behind Fred Lorz, who was disqualified for covering a majority of the track in his manager’s car after succumbing to a bout of exhaustion. The judges deemed Hicks the gold medalist in the event.

However, Mr. Hicks was not himself an innocent man. He had been “doping” with approximately 1 milligram of strychnine, raw eggs, and brandy. After his second dose of strychnine, Hicks soon collapsed, just across the finish line. Some sources state that another dose may have killed the man, but the lethal dose (at least in dogs and cats) is cited to be 0.75 mg/kg. This would assume a lethal dose an order of magnitude greater than what Thomas Hicks received. Nonetheless, we can conclude that Mr. Hicks would have been disqualified by today’s standards.

Considering that doping has been so widespread, why do we not allow it? Why do we allow performance-allowing medications, such as painkillers, but we do not allow performance-enhancing medications? With the advent of new technology, should we just accept this as a component of competition?

In a recent article, the effects of doping on at-risk populations was reviewed. I recommend reading this article to obtain a grasp of the different methods of doping. The group makes the argument that widespread doping among international athletes has spread and will continue to spread to adolescent populations. In addition to their use in sport, the adolescents use the same products for cosmetic and other non-athletic purposes. For example, steroids and human growth hormone (hGH) have been used by high school girls to reduce fat and increase muscle tone. Considering the wide range of general health and developmental dangers associated with anabolic steroids, hGH, erythropoietin (EPO), anti-estrogens, stimulants, and more, we must focus efforts on education for these populations.

Still, the debate continues. A consequence that is all too rarely ignored is that which I described above. What is not dangerous for professional athletes may prove detrimental to adolescents. Even if considered safe for all populations, use of these substances can lead to abuse without proper education in place.

Recently, the Lancet posted yet another article on Obama’s Global Health Initiative. In it, the writer points out the numerous failures of the GHI. The \$63 billion budget was not new money and was instead a new label for funds already budgeted elsewhere. Where GHI differed was in its goal to place all of the leadership under one organization. A central office was created, but this was shut down in July. The article then focuses its text on the tensions that arose when USAID took over as the leaders of the program. I could go on about the successes and failures of the global health initiatives, but I would prefer to focus on a more important issue. What are the GHIs? It is my belief that productive debate will arise if and only if we are adequately informed.

The Global Health Initiatives focus mainly on infectious disease and strengthening healthcare systems around the world. Prior to the Obama administration, they were many organizations (and if we are to be honest, still act as such). PEPFAR and the Global Fund to Fight AIDS focused on HIV/AIDS. The Global Fund also targeted tuberculosis and malaria. The GAVI Alliance put its efforts into immunization. The World Bank’s MAP dealt with AIDS and nutrition. These are not foci of the United States, and Obama’s plan called for a comprehensive effort similar to (and including) these programs that would combine their efforts to improve their effectiveness.

I will instead focus on the current administration’s global health initiative, without a critique. In November 2009, the goal of the GHI was to double US aid for global health to approximately \$16 billion per year in 2011, establish goals for the US to assist in addressing the Millennium Development Goals, and attempt to scale up domestic health efforts. The six areas of focus included HIV, tuberculosis, malaria, reproductive health, health systems, and neglected tropical diseases. The November report made three recommendations. First, the group wished to define measurable GHI targets. These would be US-specific and would focus on the delivery of care. Second, they recommended funding be increased to \$95 billion over six years, an increase from the original budget. Finally, the recommended that the GHI focus on outcomes and be people-based. Overall, the recommendations were subtle and not clearly defined, but they hinted at the theme of the GHI. The goal was to provide a comprehensive program in which the United States could better address global health initiatives. This was sold as change from the disease-specific nature of Bush’s programs to one that focused on health systems and delivery.

In July 2012, the GHI office was officially closed by the Obama administration. It was touted as a productive shift, but the reality was that this closure was due to myriad problems encountered by the program. The program lacked core leadership, and those in the developing world had troubles with knowing what defined a GHI project. While it had a huge budget, there were only four full-time employees in the office. The idea remained, but the office did not.

There is far more to this story, but that is what you should know about Obama’s GHI. It was and still is an interesting idea, but it remained an idea. What we need are solutions with better focus.

As a student of biophysics, I find myself riding the line between theory papers riddled with equations an d biology papers avoiding them at all costs. However, these types of work must be made to foster communication between fields, and I find that too often that doesn’t occur. There exists an overarching fear of mathematics in biology, and this fear must be addressed to induce discussions between members of different fields who may study similar problems.

We can address this problem in a number of ways. Theorists could avoid the use of mathematics in their publications altogether, nontheorists could study the required techniques to properly address the papers, or we could reform the educational system. The first option is an obvious failure. How can fellow scientists properly review such work without the work’s methods? Like a molecular biologist who includes protocols for every immunostain, sequencing technique, and data analysis, so too must theorists provide their techniques. The mathematics act as a prerequisite for effective peer review.

How can this caveat be overcome, then? I proposed two additional solutions, both focused on the education of the established researchers and the young who aspire to these roles. Education is not an appropriate solution, just yet. While I believe that an educated society is a successful society, this takes time. It will be decades until those in secondary school are running labs. Those who are already established do not have the time or motivation to take on new coursework, and rightly so. While the reader and the writer share responsibilities in the transport of knowledge, the writer can address this issue.

How, then, can theorists, biophysicists, quantitative biologists, and any of those who require the use of maths address this? I stated above that they cannot go without the use of equations. However, a temporary solution does exist. Here, then is my recommendation for using mathematics in biology and medicine. .

First, remove all equations from the main text. From these, decide which are integral to understanding and believing the thesis. With those, write as many out as can be accomplished in terms to which others can relate. For example, “F=ma” can be simplified as “acceleration is proportional to force and inversely proportional to mass” or “Force=mass*acceleration” to properly define terms and reduce the use of Greek or Cyrillic symbols. Grouping complex terms also helps the reader in this scenario. In a recent writeup of mine, an equation took the form, “X=c*k1*a*b*g/(k2+k3*p)” which I could simplify to, “displacement=force/stiffness” or Hooke’s Law. This grouped equation replaced my more practical (for experimentation) equation, while remaining accurate and becoming more illustrative for a reader. For all other equations, remove them. These only confuse the reader.

Where do these equations go? With the advent of electronic publications, the answer is simple. Place them in the supplementary material. Curious readers will pursue this information, and all others will not be distracted.

You may claim that doing so detracts from the paper, but I disagree. Mathematics as applied to biology should inform biologists. If few read the work due to distracting equations, communication is reduced in quality. All the information still resides in elsewhere for other theorists (and let’s be honest, collaborators and peer reviewers who already understand your work and may be familiar with the maths).

This technique makes your papers more tractable and better cited. It can lead to further collaborations. There are countless positive aspects of this technique. The only downsides of which I am aware would be the nuisance of opening the supplement and a less intimidating paper.

If your goal in science is to educate rather than intimidate, then let your writing show it.

As of this post, I have spent approximately 6-12 hours per day over the past few weeks attempting to solve minor issues in our PID controller. This required repetition of the same calibration trials daily, while I would  focus on creating a script for data analysis. It’s not challenging, and I’m used to it. However, it reveals a common issue in graduate school: we spend quite a bit of time on minutiae. For some reason, we also enjoy it.

It is this concept of delving into the abyss that I find fascinating about graduate school.