Scientific Anthology: Failure as a Stepping Stone

Introduction

Failure is often seen as a negative part of scientific discovery. Failure is inherently bad. But failure is not completely bad. When it is not a completely indomitable failure, it provides an opportunity for growth, and quite often is a stepping stone towards success, or brings you one step closer from achieving your goal.

This anthology is a collection of 15 carefully curated pieces which reflect the importance and the nuances around failure and its role in the scientific world. As you will find, failure is not only an irremovable component of science and progress, but a driving force into scientific discovery and advancement.
Example 1

A pacemaker is a battery-powered device about the size of a pocket watch that sends weak electrical impulses to "set a pace" so that the heart is able to maintain a regular heartbeat. This little device and its rhythmic corrective abilities has provided people with proper heart rates who suffer from atrial fibrillation: a type of irregular heartbeat in which the heart's upper chambers quiver, or fibrillate, increasing the risk of lightheadedness, chest pains, blood clots, or stroke. The fact of the matter is over 3 million people worldwide are using pacemakers, saving themselves from serious heart conditions that could lead to death.Such a device, however, was born from a mistake that easily could have resulted in failure.

Wilson Greatbatch was an electrical engineer teaching at the University of Buffalo where he was working on an oscillator to aid in the recording of tachycardias. He accidentally discovered the way to make an implantable pacemaker. Greatbatch made a classic dumb move: pulling the wrong part out of a box of equipment. It became a major part of saving millions of lives. “It was no accident, the Lord was working through me… The oscillator required a 10 KΩ resistor at the transistor base. I reached into my resistor box for one, but I misread the color coding and got a 1 MΩ resistor by mistake.” When he installed it, he recognized the rhythmic lub-dub sound of the human heart.Greatbatch immediately realized that this small device could drive a human heart but it wasn’t easy to find a heart surgeon who would believe in his idea.  

After failing to find a proper platform to try this experiment, Greatbatch finally found a surgeon that allowed testing to be done a dog heart. After successfully controlling the tempo of the dog’s heart, Greatbatch's implantable device of just 2 cubic inches would go onto to change life expectancy in the world forever.

http://www.inc.com/tim-donnelly/brilliant-failures/9-inventions-made-by-mistake.htmlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232561/
Example 2

David Paul Frediani committed a violent crime, murdering Helena Greenwood in 1985. Frediani did not allude prosecution from the law by eluding the police or staging his potential death like one would see in a wild TV show. Rather, Frediani comfortably lived his life for fifteen years as his incriminating DNA sat in an evidence locker, waiting to be examined. Frediani believed, although he has claimed his innocence, that evidence practically invisible to the human eye was not going to catch up to him. DNA, as he understood it, would not prove anything. Furthermore, Frediani was partially correct; his incriminating DNA left on the body of Helena Greenwood was examined by Laura Heilig in 1991, leading to no findings.

This initial failure, depending on how one would look at it, was a stepping stone for both Frediani and Heilig. Frediani lived another ten years as a free man after 1991 while Heilig continued to practice her job as a crime scene technician. Failure as a stepping stone here resulted in Heilig revisiting Frediani file in April of 1998. This time she wouldn’t fail, and she was able to implicate Frediani’s DNA that had been taken from a 1989 sexual assault database. Heilig then used this sample as a way of comparing the DNA found on Greenwood’s body. The end result was the confirmation that Frediani’s DNA was found on Greenwood’s body, incriminating him later trial. Frediani was caught and convicted more than a decade after he murdered Helena Greenwood; freedom probably never tasted better for him during that time.

The failure of Heilig in this circumstance was unfortunate because a murderer was free to kill again for years. Heilig’s inability to properly analyze the DNA sample in 1991 would only be one mistake, however, leading her to revisit the file years later. Better late than never!   

Weinberg, Samantha. Pointing from the Grave: A True Story of Murder and DNA. New York: Miramax, 2003. Print.  
Example 3

Albert Einstein was and still is known as one of the world’s most influential people. Einstein was a genius, and most people today do not realize the failures that he had gone through to attain his later success. Today the word "Einstein" is synonymous with genius. Einstein was ironically a poor student all throughout his adolescence. Einstein nearly dropped out of school because he often skipped classes and never performed well in the ones he attended. Young Einstein didn't speak fluently until he was nine-years-old, causing teachers to think he was slow. He was expelled from school for his rebellious nature and was refused admittance to the Zurich Polytechnic School.

Einstein did not only fail early on his life, but even as he entered the world or math and physics, he failed a large variety of ways. In 1905 alone, he made mistakes in: clock synchronization procedure on which Einstein based special relativity, failure to consider Michelson-Morley experiment, mistake in transverse mass of high-speed particles, multiple mistakes in the mathematics and physics used in calculation of viscosity of liquids, from which Einstein deduced size of molecules, mistakes in the relationship between thermal radiation and quanta of light, and a mistake in the first proof of E = mc2. The truth of the matter is that Einstein was no genius as society may perceive a genius to be. What made Einstein such a genius, however, was his ability to percivier despite all his failures. Einstein failed periodically in his scientific theories, but each failure was yet another stepping stone to fix his failure.

http://www.businessinsider.com/einsteins-mistakes-2011-7
Example 4



Penicillin heralded the dawn of the antibiotic age. Before its introduction there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Hospitals were full of people with blood poisoning contracted from a cut or a scratch, and doctors could do little for them but wait and hope. Antibiotics are compounds produced by bacteria and fungi which are capable of killing, or inhibiting, competing microbial species. This phenomenon has long been known; it may explain why the ancient Egyptians had the practice of applying a poultice of moldy bread to infected wounds. But it was not until 1928 that penicillin, the first true antibiotic, was discovered by Alexander Fleming, Professor of Bacteriology at St. Mary's Hospital in London. Returning from holiday on September 3, 1928, Fleming began to sort through petri dishes containing colonies of Staphylococcus, bacteria that cause boils, sore throats and abscesses. He noticed something unusual on one dish. It was dotted with colonies, save for one area where a blob of mold was growing. Fleming found that his "mold juice" was capable of killing a wide range of harmful bacteria, such as streptococcus, meningococcus and the diphtheria bacillus. This discovery eventually lead to pharmaceutical usage and distribution of penicillin that has saved lives from bacterial infections that risk becoming worse.

Alexander Fleming accidentally left this petry dish out, compromising science experiments in most instances; however, it still allowed Fleming to conduct incredible research. Penicillin thereafter took time and numerous failed attempts at becoming the drug it is today.

http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html
Example 5

Kevin Dunbar is a researcher who studies how scientists study things — how they fail and succeed. In the early 1990s, he began an unprecedented research project: observing four biochemistry labs at Stanford University. Philosophers have long theorized about how science happens, but Dunbar wanted to get beyond theory. He wasn’t satisfied with abstract models of the scientific method — that seven-step process we teach schoolkids before the science fair — or the dogmatic faith scientists place in logic and objectivity. Dunbar knew that scientists often don’t think the way the textbooks say they are supposed to. He suspected that all those philosophers of science — from Aristotle to Karl Popper — had missed something important about what goes on in the lab.

Dunbar’s findings were interesting to say the least. These professional scientists failed in a variety of ways in their experiments, and it had nothing to do with sloppiness or an apparent lack of knowledge. Rather, these experiments were for the most part designed to fail and yield results that made the scientists question their findings. Dunbar reveals that the entire point of experimenting, science, and many other endeavors in general is to fail, and to fail to a certain degree where one uses that as a stepping stone to success. Experiments in science are meant to yield the perfect results many times after that same experiment had been failed at numerous times before.  

http://www.wired.com/2009/12/fail_accept_defeat/
The Numerous Failures of Thomas Edison



Thomas Edison

Perhaps one of the best known cases of failure leading to the eventual success with the light bulb. Created in 1879 by Thomas Edison, the lightbulb remains to be one of the most important inventions within the past 200 years. Edison did not have an easy time inventing this though: he made thousands of attempts to create his first filament light bulb. The largest trouble was in finding the correct filament for the bulb. The artificial threads were not available to him since he did not hold the necessary patents. Edison went through different types of metals, papers, and woods until he discovered bamboo as a sufficient filament.  It took him over ten years and the amount of rumored attempts reaches into the tens of thousands. Despite this, Edison used these failures as progressions, slowly getting closer to his success. He used this same mentality when creating his own batteries, during which he concocted over 10,000 different combinations of chemicals in his batteries. As shown by the excerpt from his biography, when asked whether he thought that it was a shame that he had done all this work for no results, he replied, that he had found thousands of ways not to achieve his goal.  He viewed his mistakes as trials that were just as much educational as his successes. His failures provided the necessary feedback and results that led Edison to invent the first lightbulb. In this way, Edison used his failures as stepping stones towards his eventual success.

Dyer, Frank Lewis, and Thomas Commerford Martin. Edison: His Life and Inventions. New York: Harper & Brothers, 1910. Print.

Rutgers University. "The Edisonian - Volume 8 The Thomas Edison Papers at Rutgers University." The Edisonian - Volume 8 The Thomas Edison Papers at Rutgers University. Rutgers, 28 Nov. 2012. Web. 10 May 2016.

Making Safer Drugs: Failures in New Drug Development



According to Medicine.net, only 5 in 5,000 make it from preclinical to human testing, out of that even fewer are approved for people. The whole process overall can take up to 12 years to get from lab to public, during which time thousands of other drugs are denied or abandoned. The drugs that are denied are rejected due to the thousands of prerequisites and standards set by the FDA. The overall process is compiled of 7 different sections: preclinical testing, Investigational New Drug Application(IND), three phases of clinical trials, New Drug Application (NDA), and finally phase IV studies which are post-marketing studies for drugs already passed by the FDA in order to identify possible additional possible effects.  For those developing drugs, failure to be pass one of these rigorous tests does not mean it is the end of the line for that drug. Scientific researchers and developers need to continue to improve and enhance the drug in order to meet the standards set forth. Through this process of trial and revision, the drugs that make it to full public access, are fully vetted, safe, and meet a final success point where the final drug is a better product than the one before. In this way, the drug became more refined and this failure becomes the driver and the force behind creating safe and revolutionary medicine. It is failures like these which are a crucial part of the scientific world and the development of new things within the scientific realm.

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http://www.medicinenet.com/script/main/art.asp?articlekey=9877


The Search for G Protein Receptor

During an online broadcast for Science Friday, a science focused website, Dr. Stuart Firestein, professor of neuroscience at Columbia, and Helen Snodgrass talked about failure and science and one particular instance of failure acting as a stepping stone. In this section he describes the discovery of a particular kind of G protein receptor. “More than 50% of drugs on the market target these receptors. But they were very difficult to find originally, or the part of them was very difficult to find. Because the experiments continued to fail. And it turned out to be it was because of the solution they were washing the glassware in, which contained aluminum fluoride. And aluminum fluoride is an activator of these receptors, something we had never recognized. And this leads to the whole idea that trace metals are important activators of enzymes.” This important discovery is an example of when failure brought about the discovery of something that the researchers were not intentionally good for. Failure is not so clear cut, it can lead to discoveries both directly and indirectly related. Discoveries like this prove that failures can lead to success in many different ways. It is clear that failure can teach us just as much as successes and will shape and define your knowledge. Failure can create new questions and answer the ones you never knew you had. Failure like this is foundational to the learning experience and found throughout science in many different ways.

Audio Cast

http://www.sciencefriday.com/segments/why-science-needs-failure-to-succeed/
Book: Failure: Why Science is so Successful



PhD.Stuart Firestein’s Failure: Why Science is so Successful, brings an interesting thesis to the discussion of failure and science. As a follow up to his previous book, Ignorance: How it Drives Science, focuses around failure and how crucial it is to science. Throughout the novel he connects failure to success and how both are essential to scientific discovery. For Firestein, failure plays a key role in the eventual success of many different endeavors and continues to be a part of achieving any goal.  In the introduction, Firestein theorizes that not only are failure and ignorance the pillars of science, but an “engine” of science, driving it toward. Firestein, a professor of neuroscience, and the head of Biological Studies at Columbia, believes that it is just as informative as success. In the final paragraph of his introduction, he states, “ One of the things I do hope this book will accomplishes is to show science as less of an edifice built on great imponderable pillars and more as a quite human activity.” This quote is inferring more than just that failure is an essential part of science. For Firestein, failure must be a part of science because science is innately human, and humans are inevitably make flaws, they fail, it is part of life. This realization is incredibly important when approaching science. The ability to identify and realize that failure will be a part of your eventual success and to be able to grow from failure is not only important for this anthology, but an important factor in life and approaching everyday problems.

Firestein, Stuart. Failure: Why Science Is so Successful. N.p.: n.p., n.d. Print.

Photo of cover
One Man’s Failure is Another Man’s Breakthrough

 



As outlined in the Wired article, In 1964, two astronomers at Bell Labs, Arno Penzias and Robert Wilson, were attempting to create a radio telescope sensitive enough to study radiation in the Milky Way. The fundamentals of the radio telescope can be found in the video above. Unfortunately their telescope was too powerful and was picking up what appeared to be background noise. They theorized that it could be man made, such as coming from a city or nuclear fallout, but both theories fell through. In the end they ended up spending over a year attempting to solve their problem. After this period of stagnation, they decided to ask Robert Dicke, a nuclear physicist from Princeton. Dicke identified the sound as radiation from the beginning of the Universe, something which he had been looking for. They later went on to win a Nobel Prize for physics.

This is another example where persistence and failure eventually lead the scientists to a success. It may have not been the success that they were looking for but still discovered something extremely important. Like the example before, failures come in many different forms, but those failures may lead to breakthroughs and discoveries not thought of before. The failures that scientists like this face everyday are unavoidable. Though Penzias and Wilson did not create their hypersensitive radio telescope, they were able to learn more about radio telescopes and what was causing their static.

Lehrer, Jonah. "Accept Defeat: The Neuroscience of Screwing Up."Wired.com. Conde Nast Digital, 21 Dec. 2009. Web. 10 May 2016.

http://www.wired.com/2009/12/fail_accept_defeat/all/
Cnadian School: Before the Hippocratic Revolution



When we examine the history of medicine, most people accredit the Greek physician Hippocrates as the father of modern medicine. There have been many failures when it comes to the history of medicine. Before Hippocrates made the discoveries that we know of medicine today, he attended the Cnadian School. The failure in the Cnadian school’s approach was due to their thinking that organs in the body were isolated. In other words, they did not believe that when disease affects one organ/area it could spread to other areas of the body. This would lead physicians to ignore certain signs and symptoms, and falsely diagnose their patients.

After several failures as a result of the schools teaching, Hippocrates came to disagree with many of the school's beliefs. He believed the human body functioned as a unified organism “physis”  and that the body must be treated as a whole. In his research and work focusing on physiology and pathology, he discovered the concept of the Four Humors.

The Four Humors

The studies of Hippocrates says “health is the balance of of the Four Humors. Disease results from their disharmony and imbalance.  The physician's job is to restore health by correcting the imbalance and restoring harmony to the humors.” In treatment, Hippocrates was conservative and moderate in his approach opposed to radical and extreme which is a route scientists might choose when they are trying to disprove failure. He prescribed medications that would resist and overcome the organism triggering the disease rather than just focusing on the area that seems most affected.  He did not abuse bloodletting, the surgical removal of some of a patient's blood for therapeutic purposes, like many physicians of his time. An interesting video (0:00-6:15)of the ancient practice outlines its previous use. Instead, he prescribed diet, gymnastics, exercise, massage, hydrotherapy and sea bathing depending on the ailments of the patient. Hippocrates used the failures of the Canadian school to better his role as a physician and actively seek out ways to take care of the ill, and prolong life spans. His use of rational science is one we model after today.
Challenges in Synthetic Biology



Scientists are constantly trying to change the face of medicine by creating new synthetic drugs that will improve the standard of living for affected populations. However, there are major challenges that face the scientists researching in the field of synthetic biology. This article states that it is difficult “to engineer life to be a predictable tool.” Because living organisms are to manipulated for practical means, it is not easy to predict their behavior. Scientists may encounter failure when genetically modifying the cells of food, medicine, different environmental factors and microbes. This makes room for errors because cells are messy and can evolve in new ways. For example, the backbone that makes DNA is what scientists try to make physically in order to.copy the amino acids and create duplicate backbones. They have even learned to expand the DNA alphabet. These new genes are constructed on a computer, and are constructed to make the chemical backbone sturdier and less susceptible to degradation. Some advancements have been antimalarial drugs, and creating different bacteria and yeast from scratch.

The failures appear in the labs when cells acquire random mutations in their DNA, or when some cells produce more offspring than others or completely die off. The results in slight changes from generation to generation, but this is frustrating to scientists who wish to design cells to perform a specific task in a pharmaceutical factory. The slight setbacks from random mutations lead to more serendipitous discoveries that can help the original cause at hand. This is why scientists should be prone to failure and have open options.
Marie Curie

marie_curie_colorcurie_diploma

Marie Curie was a woman of science who focused in researching radioactivity. Born in Poland in 1867. She lacked opportunities to pursue her interest in science due to her status as a woman, but especially as a woman of a poor socioeconomic status. Her perseverance to learn and provide the funds to attend university is the same perseverance she demonstrates in her research. Her research of uranium led to her discovery of  the two elements radium and polonium. It took her, and her husband Pierre, 3 years to discover the elements. In those years she and her husband Pierre were forced through the years to constantly publish research, even through years of failure. Her research and discoveries earned her a Nobel Peace Prize in 1903. She knew the radioactive elements could be used to treat cancerous tumors, and she willingly exposed herself to radiation to test their efficiency.With Marie Curie’s biggest accomplishments her failures also shine through. She and her husband, Pierre Curie, met unfortunate demises that undermined their brilliance in their scientific breakthroughs. Her death was said to be caused by aplastic anemia, a disease of the bone marrow. It is likely that the radioactivity she had been exposed to during her career caused the disease.

Marie’s failures came slightly during her research of radioactive elements, and whenever she did not discover what she intended- she would wonder upon another stepping stone that would grant her a closer look into the radioactivity. An example of this would be the liquid which was the remnants of pitchblende. The ironic work of the Curie’s could kill if one was not protected, but cure deadly diseases.
Errors in Surgical Procedures: Fistulas

AV shunt(1)

Surgeons are often faced with many challenges during surgery. A common challenge is a complication known as a fistula. A fistula is an abnormal connection between 2 body parts, such as an organ or blood vessel and another structure. Fistulas are usually the result of an injury or surgery. Infection or inflammation can also cause a fistula to form. Fistulas would often occur after seemingly simple surgeries, such as kidney transplants but surgeons would encounter during surgery and postoperative. Fistulas may occur spontaneously, as a result of tumor, irradiation, or inflammation.  However, efforts to avoid this failure have resulted in the an article on the errors of the research AV fistulas remarks “Despite the generally low rate of complications of native AVF, early failure within 1 month has been observed in some series in up to 29% of patients.  Early failure, defined as non‐function of the AVF, is mostly caused by early thrombosis secondary to errors in surgical technique. Thoughtful analysis of the techniques of surgical creation of an arteriovenous anastomosis has identified a number of potential errors which may contribute to such early failure.” These AV fistulas have been a discovery to aid in the fight of sepsis and death by enterocutaneous fistula. Surgical errors are understandable, and are high motivations to succeed because it is often life or death on the table. Surgeons research, vehemently, to discover what went wrong, and their solutions on how to correct their mistakes often means granting a prolonged life to another patient.

Professor David Colquhoun: Clinical Trials



Professor David Colquhoun is a British pharmacologist who often critiques the work of alternative medicine.  The rate of late stage clinical trial failures is the single biggest determinant of returns on pharmaceutical R&D. "The lion’s share of discovery and development costs come at the end of the process, and if those trials fail (whether for safety or lack of efficacy), all the capital invested up to that point is lost." (Grainger). There are many false positives, false negatives, and true positives that can be generated from experiments. Especially for rare and specified research.

The entire early development process, therefore, is designed to de-risk those large and expensive pivotal trials that can lead to approval and sales.   Smaller and cheaper clinical studies are meant to predict the outcome of the larger, more costly ones to come. There may be more pressure to succeed because there are costs backing up research, but failures cannot be avoided. It is agreeable, that the failure rates can be too high that consideration of cutting funding may be necessary. But when can that call be made, when life-saving techniques are being researched?

This example serves as a critique of failure and why it is acceptable to an extent. It also gives a reason as to why failure is a natural factor of clinical trials. The nature of a clinical trial gives way to error because it is so experimental. However, with rates of failure so high in drug discovery and development can it be blamed on the clinical trials? Colquhoun disagrees and says "by thinking carefully, searching the literature and conducting a proper assessment of the likelihood of success before committing to test a hypothesis" it will lower the false discovery rate and save money. 
Conclusion

In the end, it is noticeable that through several discoveries in science; Failure is a pertinent stepping stone to success. Though it may be discouraging at first, failure can be used as a motivator to discover beyond what was originally intended, it can even make way for multiple results needed for your original search. As Steven Johnson explains in his book Where Good Ideas Come From “ Being right keeps you in place. Being wrong forces you to explore” (Johnson 137) Failure is one of the building blocks to success, and it may be a slow, winding road filled with several road blocks, but failure and success are closer neighbors than one would think.
Scientific Anthology: Failure as a Stepping Stone

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