How YOU can help science by solving puzzles

The last few posts were mainly focused on concepts in science but today I just want to let everyone know of an easy way of helping biological science. The folding and conformation of proteins is essential for their function. From the DNA sequence, we can translate out of which amino acids the protein is made up and in which order they have to go. But the final structure is much more complicated to understand because a larger number of chemical bonds and interactions have to be take into account.

The program Foldit is a distributed computing application (like SETI@home where unused processing time of your computer is donated to sorting through radiotelescope data.) The difference between SETI@home and Foldit is that Foldit is looking to the smaller structure and therefore inward instead of outward. Foldit tries to simulate how a protein will fold when it is finished. The computer time you donate will be used to calculate the possible and impossible conformations for the protein.

Even better, you can even interact! Foldit is not a passive activity but fully interactive. because they are also trying to see if humans can improve computer predictions. Each protein is given to you first in an unfolded version (much like the translated product coming from the ribosomes). With a few tutorials and tools you are already able to fold proteins in their proper and most stable form. The picture below shows you the beginning of protein puzzle 48 (taken from Fold.it, links below).

The goal now is to fold it into the correct conformation as seen below.

Try it for yourself and see if you like it. Maybe next time instead of solving a crossword puzzle or doing a Sudoku, try folding some proteins and help science!

Koch's Postulates

In my last post I was describing how scientists use the scientific method to keep their research objective. One of the best examples of applying the scientific method are Koch's Postulates. Robert Koch (1843-1910, left) was a german physician who was interested in how diseases are spread. He is considered the founder of modern microbiology and bacteriology together with his contemporary, Louis Pasteur (1822-1895, right).

In the course of his career, he developed countless microbial techniques that are still in use today. The Petri dish is named after his assistant. He identified the causative agents of Tuberculosis (Mycobacterium tuberculosis), Anthrax (Bacillus anthracis) and Cholera (Vibrio cholera). This earned him the Nobel prize for medicine in 1905.

One of his greatest contributions to microbiology was the formulation of the four Postulates that now carry his name. The postulates are step wise, each postulate based on the previous finding.
In order to establish that an organism causes a disease the following requirements have to be fullfilled:

Step 1: Association- The organism and the disease are observed together consistently.

Step 2: Isolation - The organism can be isolated from the diseased.

Step 3: Inoculation - The isolated organism causes the disease in a healthy individuum.

Step 4: Re-isolation - The organism can be re-isolated from the infected individuum.

Now look at each of these steps carefully and think about what they require you to do. Did you notice it? Between each of the steps the principles of the scientific method are applied. Here is a more graphic representation of the application of Koch's Postulates.

By putting clearly defined rules for what defines a disease causing organism (today referred to as a pathogenic organism or just pathogen), Koch made a major contribution to the then raging discussion about the cause and origin of diseases.

Before Kochs discovery of the Cholera bacterium, there was a heated discussion between the Contagionists and the Anticontagionists. The Anticontagionists (Max von Pettenkoffer was one of them, see also this post) argued that in their theory human-to-human transmission was only a very minor component. They were strong opponents of quarantine and disinfection because it inhibited trade and was less effective than local solutions like improved sanitation. You can read more about it here.

Koch's Postulates proved that transmissibility played an important role in epidemics and quarantines and disinfection was indeed a suitable method to counter both. In the end, everyone benefited from the discussion because it improved both local and global safety against infectious diseases. Getting scientists to agree to something is quite difficult but using the right arguments derived from proper use of the scientific method and you have a good chance of succeeding.

Next week I will write about the central dogma of molecular biology and why it is not so dogmatic anymore.

The scientific method

In my previous post I was talking about the difficulty that scientists face to keep their research objective and unbiased. Luckily, smarter people than me have developed a basic set of concepts that help do that. All these concepts are mainly based on the Aristotelian laws of logic from the third century BC. Most of the ideas that define the scientific method nowadays are already described there. The scientific method is at the heart of science as a set of rules to make research as objective as possible. It is usually described in four basic steps.

Step 1: Observation and description of a phenomenon or group of phenomena.

Step 2: Formulation of a hypothesis to explain the phenomena.

Step 3: Use of the hypothesis to predict the existence of other phenomena, or to predict quantitatively the results of new observations.

Step 4: Performance of experimental tests of the predictions by several independent researchers and properly performed experiments.

Actually, people use these steps almost instinctively to predict cause and effect and adapt accordingly. For example, when you wake up in the morning, you look out of the window and see people on the street in cold weather clothing (Step 1, observation). Your hypothesis (Step 2) is that people are wearing warm clothes because it is cold outside (Step 3, prediction). To test your prediction you open a window or look at a thermometer (Step 4, Experiment). Usually the laymen abstain from enlisting independent researchers to do control experiments.

The scientific method has been refined over the centuries but the core of it is still untouched. The setup that is usually used as a checklist for adherence to the scientific method is the following:

1. Define the question
2. Gather information and resources (observe)
3. Form hypothesis
4. Perform experiment and collect data
5. Analyze data
6. Interpret data and draw conclusions serving as a starting point for new hypothesis
7. Publish results
8. Retest (frequently done by other scientists)

Notice point 6 which clearly shows that you normally refine your hypothesis based on the outcome of your first results. Most hypotheses defined by scientists continuously cycle between step 3 and 6 before they are ever published. The picture below describes the usual approach.

It is also important to note, that the scientific method doesn’t allow the absolute verification of a hypothesis. Einstein himself said: "No amount of experimentation can ever prove me right; a single experiment can prove me wrong." Especially physicists have a tendency to postulate an unknown factor, like the Higgs-Boson, to resolve issues with current theories. The current interest at the large colliders in Switzerland (Large Hadron Collider, CERN) and the US (Tevatron, Fermilab) is to experimentally proof whether or not the Higgs-Boson actually exists and has the properties that are required to make the theory behind it work.

If the Higgs-Boson could not be experimentally proven in the predicted range, most theoretical models of physics would have to be reexamined. I think that makes it slightly more understandable why there is so much money going into this kind of research because entirely rethinking physics sounds like a huge headache to me.

You can easily test what I said about the instinctive use of the scientific method. Just watch yourself and observe how your brain works and you draw conclusions about your environment. Or ask people how they arrived at the conclusion that it won’t rain today. But don’t let them get away with: “It never rains when I have an umbrella with me.” Maybe you can disprove that to them using the scientific method.

Have a nice weekend and keep on thinking!

The above video was made with a 250,000 fps camera and captures a catapulting spore from a fungus. The organism, Pilobolus crystallinus, or more precisely - its spore, is said to be the fastest living thing in nature.

Here's a fragment from Richard Hammond's Invisible Worlds featured documentary on the same story:

Personal opinion and bias in science

In my last post I was writing about how scientists are constantly looking for the big picture and more pieces of the puzzle. But how do we do that? What tools and techniques do we use? In the future we will describe specific techniques like imaging or mass spectrometry in this blog. But for now I would like to give a short introduction into the theoretical groundwork that every scientist uses. I hope that by explaining basic concepts in science it will help you to understand (and reality check) some or most of the news items that are published in non-scientific journals.

I often read something in the news about science that looks like a brilliant breakthrough and the journalist tries to suggest immediate applicability. In most cases it is just not as simple as that (especially not if it is written in the tabloids). Just because something was tested and worked in an animal model does not mean that it will work in exactly the same way in humans or soon. Sometimes it even has detrimental effects (London drug trial incident 2006). So I would like to explain a few basic concepts in science in my next posts. But first I want to highlight some problems that scientists face not only from without but also from within.

A major problem in science was (is?) the removal of personal opinion and bias. At some point people can get so invested in their idea that any other theory, observation or result must be wrong and can be explained away or faulted for some reason in some way. One of my favorite examples is the feud between Robert Koch and Max von Pettenkofer about the transmission of Cholera. Both brilliant scientists in their own right, they could never agree if Cholera, as it had been shown by Koch, can be transmitted from person to person and cause disease. This is one of Koch’s postulates, which I will address in a later post. Despite experimental evidence, Pettenkofer, aged 74, drank a pure culture of Vibrio cholerae, to show his opponent once and for all. He survived and just contracted light diarrhea and abdominal pain (he probably had contracted Cholera earlier in his life and this led to a lighter course of disease this time around). Pettenkofer saw that as irrefutable evidence that Koch was wrong.

Today we know differently but despite the fact that Pettenkofer was wrong in this instance he still was a brilliant scientist and one of the most important hygienists. The history of science is full of stories of personal animosity, spite and (now) hilariously wrong explanations. So besides being curious (as I stated in my last post), scientist also need to be critical. And first and foremost critical of their own work. If you can’t convince yourself based on your data how do you expect to convince others? Being impartial and objective is hard for everyone, but as a scientist it is even more important to not get too attached to your ideas and theories. Because they are just that until you have proof and other scientists can reproduce your results. I will also explain and discuss the peer review system in place for scientific journals which is trying to safeguard science against fraud.

But I think it is also very important that scientists adhere as strictly as possible to the scientific method, which I will discuss in my next post.

Clemens J. Heilmann

P.s.: Opinions, suggestions, theories, comments? Please let’s hear them below.

Motivation to do science

First of all, I would like to welcome every reader to our blog. We hope we can interest you at least a little in science and make it more understandable why people in the prime of their live like to spend time day, night and weekends in labs and in front of computers instead of partying and just having a good time. But actually, to be honest we do have a good time. And here is why…

The way people get into science is very diverse but we all share on basic trait that a scientist can’t do without, curiosity. Curiosity killed the cat but luckily the cat has nine lives. This analogy is actually truer than you would think. One of the first things you have to learn to deal with in science is failure. And frustration. So if you are not curious or enthusiastic about science you probably won’t make it. One of the things I think makes a good scientist is the ability to ask the question everyone in the room is thinking about but no one dares to voice. Call that curiosity for lack of a better word.

Children are the quintessential scientists. Full of enthusiasm and an insatiable curiosity for the world that surrounds them, they go forth and explore their world. And this curiosity is the hardest thing to conserve when you get older. Other, more important things start to enter the equation of what makes our life successful (family, money, power). So science is also escapism in a way. Because despite its rigorous rules for publication and proper research, most scientists are whimsical, funny and most importantly, curious. Basically, scientists didn’t really want to grow up but still made something out of their natural strengths.

But why do we accept to bear the common failures and frustrations of daily lab work? I think the reason is that we want to understand and we love it when all parts of a puzzle come together and form a stunning no picture of the world that surrounds us. And we are the first to have a glimpse. This glimmer of knowledge is what we are after. If you look into the past, you will always see that science is the great door opener to improving the human condition. Curing numerous diseases, developing clean, sustainable sources of electricity, increasing the quality of life for everyone on this planet are some of the key challenges for humanity. Science can solve or at least help to solve most of them.

Most scientists are not Marie Curie, Robert Koch, Louis Pasteur or Leonardo da Vinci. But we all strive for that flash of genius and that brilliant deduction about the world that surrounds us. Whenever we understand something, we want more. And we never give up. We always look for the next puzzle to solve or when we solve one, we only see it as a small part of an even bigger picture.

Clemens Heilmann