Big, Expensive Pharma

By: Ben2015 5-21 Blog 4
Image by: Amber D. Miller

In 1937, a pharmaceutical company wanted to make a kid-friendly, raspberry-flavored liquid version of the antibiotic sulfanilamide. Unfortunately, because of the chemical properties of this antibiotic, they couldn’t just dissolve it in water. Instead, they decided to use diethylene glycol, a liquid chemical with a sweet taste kids love. Diethylene glycol, commonly known as antifreeze, is a liquid normally put in cars to prevent the engine from freezing. Shortly after sales began, over 100 kids died from taking this medication. Congress responded by passing the Federal Food, Drug, and Cosmetic Act in 1938, giving the Food and Drug Administration (FDA) the power to test the safety of drugs before they came on the market.

The FDA has a long, rigorous approval process for bringing drugs to market. Drug companies extensively screen millions of compounds to find any with specific molecular activity. They test any active compounds they find in cells, and then in animals, both for safety and activity. Finally, they have to conduct three phases of clinical (human) trials:

Phase I: Is it safe? The drug is tested on 20-80 healthy people to make sure it doesn’t cause any major health problems. This is also when they figure out the right dose to give patients.

Phase II: Does it work? The drug is tested on 100-300 people with the disease it is intended to treat. Only half the patients receive the drug, while the other half get a placebo (sugar pill). Then, the clinicians compare the number of patients treated with drug who get better versus the number of patients with placebo who get better. Common side effects will become evident at this stage. If more people get better taking the drug than taking the placebo (without any debilitating side effects), they can move on to the next phase.

Phase III: Is it really safe? Now comes the large-scale clinical trial, where 1,000-3,000 people get either the drug or a placebo. Treating a large number of people allows for identification of less common side effects.

At this point, the drug can be approved and sold, though only with a doctor’s prescription.

But wait, there’s more!

Phase IV: Are there any extremely rare side effects? Many drugs will continue to be studied after they are on the market in case the previous trials missed anything. Let’s say a drug kills one in 1,000,000 people. You’re unlikely to see that if you’ve only tested the drug on 4,000 people. The FDA can and frequently does take drugs off the market if they fail a Phase IV trial.

This entire process typically takes about 14 years and $1 billion to get a single drug to market. That is why drugs are so expensive. Although a company could manufacture a month’s worth of pills for $1, they are trying to recoup the money they spent getting the drug approved in the first place. They even have a time limit on this. When a company gets a drug patent, they have exclusive rights to manufacture that drug. But after 25 years, the patent expires and another company can make a “generic” without having to go through the same FDA approval process. Generics are the exact same chemicals, but companies can sell them for much less. Sometimes a big company will buy up a smaller company with a patented drug that has already gone through clinical trials, thus skipping the initial expense. Some pharmaceutical companies will also make deals with other companies to prevent them from making generics after their patent expires, which would drive down the price.

Because of the long, expensive road to approval, these companies wouldn’t spend $1 billion unless they thought they could make that money back. It’s important to keep in mind that a pharmaceutical company is just like any other company. Their goal is to make money by producing and selling a quality product. The FDA only officially approves each drug for specific medical applications, though doctors are not legally limited to FDA-approved uses for each drug. This is also why you see so many commercials for prescription drugs. Pharmaceutical companies want as many people as possible to buy their drugs. Even though you can’t go to the store and buy them yourself, the companies want you to bug your doctors to prescribe their drugs. Direct-to-consumer advertising of pharmaceuticals has been around for less than 20 years, and is only legal in the US and New Zealand, but these companies continue marketing this way because it works.

So if drug companies are trying to convince you that you need their drugs so they can make money, how do you know which drugs you really need to take? The most important part of drug treatment (all treatment, actually) is having the correct diagnosis. Once diagnosed, your doctor will often be able to recommend the most appropriate treatment based on your age, specific symptoms, lab test results, and a host of other factors. So start with the doctor, not the drug.

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Personal Police Force: The Immune System and Vaccines

By Meg-alodon
Image by: Amber D. Miller

2015 5-21 Blog 3Vaccines and infectious diseases have been in the media rather frequently of late, especially with the measles outbreak in California and the recent elimination of rubella in the Americas.  Most of us have been told that vaccines are beneficial and that they help prevent illness and stop epidemics, but how do they do that?  How do vaccines work to stop us from getting sick?  To answer that question, we’ll have to dive into one of my favorite topics – immunology, the study of the immune system.

The immune system is one of the most fantastic parts of us.  It is the reason why we are able to survive in the world without succumbing to infection every 10 minutes.  It is the reason why, when we get sick, we are able to fight off that sickness and return to a healthy state again.  The immune system is the police force of our bodies, protecting our insides from dangerous criminals of the outside world.

These criminals may take on many forms.  The most common of these criminals (at least in the developed world) are bacteria and viruses (although occasionally we experience attack from fungi or parasites).  Bacteria and viruses are both microscopic organisms; they are too small to see without a microscope, and most viruses are too small to even been seen with a microscope.

As I mentioned earlier, the immune system is the police force of our bodies.  There are two main branches of the immune system: the innate immune system and the adaptive immune system.  The innate immune system is comprised of many different types of white blood cells that act as patrolling police officers.  Cells of the innate immune system continually move through the body via blood vessels and lymphatic vessels (specially designed fluid drainage routes).  In contrast, the adaptive immune system is made up of white blood cells that remain at the police station (lymph nodes) until called into service by the innate immune system.

When bacteria or viruses invade our bodies, they are recognized first by the patrolling cells of the innate immune system.  The immune cells distinguish between invading bacteria or viruses and human cells based on common identifiers present on bacteria or viruses but not present on human cells.  It would be like if all criminals wore purple fuzzy hats, and all law-abiding citizens did not; the police would be able to pick out criminals based solely on whether they were wearing a purple fuzzy hat.  The same holds true for bacteria and viruses, which often wear different proteins or sugars than those that are found on human cells.

The innate immune system is able to eliminate most invaders without involving the adaptive immune system (officers at police headquarters).  These officers have very unique ways of eliminating these threats.  Some officers (macrophages) will eat the criminals in a process that is fancily named phagocytosis.  Once inside the macrophages, bacteria and viruses will be dissolved in acid pockets called lysosomes.  Other officers (neutrophils) will explode near bacteria and viruses, coating the invading criminals with toxic chemicals.

The innate immune system is not able to contain all infections, though.  Sometimes, this is because of the number of bacteria or viruses entering the body.  More often, though, it is because bacteria and viruses find ways to circumvent the defenses of the innate immune system.  In these cases, the adaptive immune system is crucial to ending the infection.

Most cells of the innate immune system can also function as evidence collectors and will present said evidence to the cells of the adaptive immune system stationed at the lymph nodes.  Cells that act as evidence collectors are termed “antigen presenting cells.”   Antigens are small pieces of sugars or proteins that cover bacteria and viruses. Antigen is evidence that can be used to identify a particular bacteria or virus, similar to a fingerprint.  When presented with these fingerprints, the adaptive immune system jumps into action.

There are two main cell types involved in the adaptive immune system: B cells and T cells.  B cells could be described as weapon specialists.  They create antibodies, which act as homing devices to the antigen of bacteria or viruses.  These antibodies circulate through blood vessels and will stick to the appropriate antigen.  Antibodies bound to antigen tell the innate immune system to launch an even stronger attack against the invaders.

T cells can perform two main functions.  Some T cells will perform more managerial tasks.  They give instructions to B cells, other T cells, and other immune system cells.  Other T cells are responsible for interrogating our bodies’ cells, searching for viruses and other pathogens which may be hiding within our cells.  Remember how bacteria and viruses have their own fingerprints (antigen), so to speak?  Our cells also have fingerprints too, but when infected by viruses, our cells will often display viral fingerprints instead of cellular fingerprints.  T cells can recognize the difference between own our cellular fingerprints and those of bacteria and viruses.  T cells can also force any cell in our body to show its fingerprints.  If a T cell finds a cell expressing viral fingerprints, the T cell will kill the infected cell.

To recap everything about the immune system thus far, the innate immune system are the patrolling officers, capable of dealing with some invading criminals on their own.  Particularly numerous or sneaky criminals often require the adaptive immune system to eliminate them.  Antigen presenting cells present evidence to the adaptive immune system, which can then form homing devices (antibodies produced by B cells) or interrogate our cells searching for virus (T cells).

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Now that we’ve discussed how different aspects of the immune system work, how does this apply to vaccines?   When you get a vaccine, viral or bacterial antigens are injected into your body.  Antigen presenting cells present these antigens to B cells and T cells.  Each B cell and T cell recognize one specific antigen, and this recognition allows the cells to perform their duties and to survive for many years.  These surviving  cells will remain in the lymph nodes and wait for a similar criminal to come again.  This process is called immunological memory: the immune system remembers past criminals and mobilizes its officers to eradicate future criminals before they can cause disease. Immunological memory occurs after both illness and vaccination; however, vaccination allows for memory to develop without illness occurring.

Vaccines allow the adaptive immune system to prepare itself for a potential upcoming infection.  Thus, if we were ever to encounter said virus or bacteria, our adaptive immune systems would be ready to defend our bodies, and we would avoid dangerous illness.

For more information, check out the following website:

How Stuff Works – The Immune System:
http://health.howstuffworks.com/human-body/systems/immune/immune-system.htm

No Money for Young Investigators: Uncertainty for the Future of Science

2015 5-14 Blog2 smaller

By: Michelle Rubin
Image by: Amber D. Miller

In 1993, 34% of PhD students entered tenure track positions. In contrast, only 23% of students joined the academic field in 2012 (Rockey et al., 2012). As a PhD student, I know many of my fellow students come to graduate school with the intention of going into academic research. However, after a few years, they realize that the number of PhD students graduating greatly outnumbers the positions with available funding for young investigators, and academia may no longer be a viable option. NIH director Francis Collins recently spoke about precisely this problem. “Many young investigators are on the brink of giving up because of the difficulty of getting support,” he asserted in an article published in USA TODAY (Szabo, 2014).

We are losing promising and innovative ideas due to budget cuts. We should fear for the future of academic research.

The Nobel prize winning research on fluorescent proteins, a technology now commonly used in biomedical sciences, could not have come about without the funding of a young investigator at the beginning of his career. Martin Chalfie, among others, manipulated and adapted the jellyfish-derived Green Fluorescence Protein (GFP) for use in a variety of biological systems (Chalfie, 1995). This innovative but risky work would not have been possible if Martin Chalfie had not been funded as a young investigator. He had no guarantee of success in his adaptation of GFP into heterologous systems in his later career. We could lose these kinds of discoveries if we fail to  fund young investigators with feasible but out-of-the-box ideas.

Between 2010 and 2014, the number of new investigators funded by NIH grants fell from 2,100 to 1,600 (NIH, 2014). This means that 400 new young investigators with creative ideas were not given the opportunity to achieve success. Consequently, we may have already lost brilliant ideas for treating bacterial or viral infections, cancer, or for developing new technologies to use in biomedical research. Between 1996 and 2010, the number of young investigators (age 35 or younger) that obtained new grants fell from 6.0% to 2.0% (See graph, NIH, 2014).  However, the worst blow came in 2013, when the NIH budget was cut by 5%, meaning that 640 fewer grants were given out in 2013 than in 2012 (Kuehn, 2014). A major consequence of this lack of funding is emigration of young investigators from the US. As Dr. Collins noted, “up to 18% of young investigators are leaving the US”(Szabo, 2014).

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Certainly not all grants or new investigators have ideas that should be funded. Representative Jack Kingston, chairman of the House Appropriations subcommittee, wrote in a letter to Dr. Collins, “I support the NIH’s core responsibility of basic research, but believe it should stop the frivolous, politically-motivated, and wasteful grants it has been funding” (Szabo, 2014). Although it is crucial to critically read and assess all the grants given by the NIH to investigators, it is just as important to fund new and exciting ideas.

It is impossible to demand that the US government give the NIH more money, but there are alternatives. After ending the prolonged operations in Afghanistan and Iraq, the Department of Defense has proposed reducing their budget by $75 billion over the next two years (Simeone, 2014). Some of these funds could be reallocated to the NIH to help reduce the impact of the 2013 budget cut. Even though not all this money can be given to the NIH – after all, there are multiple agencies within the US government that require funding – a small injection of funds into the NIH would allow a greater number of innovative but risky grants to be funded. This would help young investigators with promising ideas to start their laboratories.

Better funding additionally changes the mentality of PhD students. As students see young investigators leave the country or shut down their laboratories due to lack of funding, they decide to not pursue academic careers in the future. By using a small portion of the money that previously went to the DOD budget for the NIH budget, young and new scientists can continue to be creative without fear of losing their jobs in the future. After all, we never know who might think of the next staple in biomedical research or the next treatment for cancer.

We are not Ozymandias

blog_1By: The Motley Advocate
Image by: Amber D. Miller

In 1817, Percy Bysshe Shelley wrote the acclaimed poem Ozymandias. Some of you may be familiar with the DC Comics Character of the same name, while I imagine many of you recognize the name from the show Breaking Bad. The famous poem describes the toppled statue of an Egyptian king. Although the statue is in ruins amidst the long destroyed kingdom, its pedestal still reads, “My name is Ozymandias, king of kings: Look on my works, ye Mighty, and despair!”  The character in the poem is considered the essential example of how the mighty have fallen.

For me, Ozymandias is an important reminder of ethos. There are three modes of persuasion to appeal to an audience: logos, pathos, and ethos. While logos and pathos are an appeal to logic or emotion respectively, ethos is an appeal to credibility. Essentially, it is where an author argues he or she should be allowed to speak because of who they are. Authors must establish themselves as credible sources.

Before I go any further, ethos is not a bad thing. When we are young most of us listen to our parents because of ethos. Children may not understand that a dead bird could make them sick if they touch it (logos), but they may listen to their parents simply because they are adults (ethos). If you see a police officer telling people to leave a building, you listen because of his or her authority as a police officer. If a person has worked at a zoo for 10 years, I would listen if they say it is dangerous to provoke the tiger.

However, ethos can sometimes turn people into Ozymandias. They claim to be a king, but when we look around at their kingdom, we realize they are king of nothing. Essentially, they claim to be a credible source when they are not. For instance, scientists often dislike it when politicians and celebrities make statements that they claim are “fact” but are untrue or not supported by any evidence. It’s mainly frustrating because fans will decide the celebrity is correct just because he or she is a celebrity.

Once again, this is not always a terrible thing. Fame can be a powerful force for good, as long as the people are well informed about the real facts. Seth Rogen used his celebrity to speak before Congress about Alzheimer’s disease, not claiming to be an expert of the field, but giving testimony about his mother-in-law and how the disease has affected their family. Kristen Bell has written a well-researched article about being a mother trying to decide if she should vaccinate her children. In this article she “shows her work”, drawing her information from scientific research and not just her own opinion. No matter how you personally feel about these issues, it is commendable that these people relied on more than just their own celebrity status when presenting their arguments.

From the other side, remember to not be Ozymandias when presenting your argument. Let’s pretend for a second that the kingdom of Ozymandias was not in ruins, but just hidden in the desert. Someone traveling through the desert would assume the kingdom did not exist, simply by looking at the broken statue declaring itself the king of kings. To me this is the same as a scientist trying to convince someone about a topic by declaring, “Look, you should just trust me because I’m a scientist.” I can fully respect people who respond by saying, “Why should I take your word on the matter, I want to see the facts myself.” In fact, that’s what scientific publication is all about, showing the data.

Now I can understand how easy it is for any of us to do this. Think about your job, and try to explain everything in a few sentences. It can be challenging. It is really easy to say “I’m a doctor; you just need to trust me. I’m a plumber; you just need to trust me. I’m an accountant; you just need to trust me.” The longer you study the subject, the easier it is to claim, “I’ve studied this for x years; you just need to trust me.” And some people will. If you get the chance to speak to a researcher who has been studying a disease for half of their life, they really do understand the disease. However, some people need more information, because they want to understand for themselves. For these people relying on ethos will not work.

In life, you need to watch out for Ozymandias. Don’t assume that someone is an authority on a subject just because they are well known. On the other hand, don’t assume everyone in a place of authority is lying to you. Remember, the power is with you.  Does the speaker have credibility for this subject? Do the facts agree with what they are saying? Just use discretion about who you are listening to, examine the kingdom they claim to rule. After all Ozymandias said “Look on my works, ye Mighty…” Just don’t despair.

References:

1. http://www.bbc.co.uk/arts/romantics/shelley_ozymandias.shtml
2. http://dc.wikia.com/wiki/Adrian_Veidt_(Watchmen)
3. http://entertainment.time.com/2013/09/16/ozymandias-what-does-that-breaking-bad-episode-title-mean
4. http://www.bbc.co.uk/history/ancient/egyptians/ramesses_01.shtml
5. http://pathosethoslogos.com/
6. http://www.cbsnews.com/news/seth-rogen-pleads-congress-over-alzheimers-slams-low-senator-turnout/
7. http://www.huffingtonpost.com/kristen-bell/vaccines-are-safe-and-facts-are-your-friends_b_7083504.html?1429233999&ncid=tweetlnkushpmg00000067