After I put down the phone, my heart never felt so heavy. I just called my parents in my hometown, Chengdu, a city with 12 million people, which is just 90 kilometers away from the center of the strong earthquake at a magnitude of 7.9. It has killed more than 10,000 people so far. The death toll is still rising hour by hour.

Fig. 1 Earthquake map by the United States Geological Survey

At around 2:30 PM Beijing time today (May 12), a terrible beast began to shake the city furiously for about two minutes. Since it was still school time, hundreds of children in some middle schools were suddenly buried over when the campus building totally collapsed during the strong shake. Thousands of survivors from their destroyed houses were bought to the open places near the hospitals to receive some simple treatments to prevent from further bleeding. They varied from old women in their 80s to Children who are only several years old. Hospitals themselves are no longer safe since more earthquakes could come at any time, thousands of patients were also persuaded to leave hospital buildings and stay in the open places around. Even new born babies were also taken out with intensive cares from nurses nearby. Not like people in California, people in West China have no experience of the earthquake in the past 30 years, let alone for this strong one. Millions of people dare not back to their home for sleeping at night. They simply slept on the street or the city squares with light around to drive away their fear and anxiousness. Government began to set up large tents as the temporary shelters, and offer food, water and blankets etc. for all those suddenly homeless people.

Fig.2 Rush wounded students to the hospital

Fig.3 New born infants being taken out

Chengdu is by no means the worst-hit place in this disaster. In a single county nearby, more than 7,000 people were reported being killed so far. The highways and railways to the cities near earthquake center were heavily blocked by huge rocks fallen from the landslides nearby. All communications, either landline or mobile, had been totally cut off. Nobody knows what had happened to the city named Wenchuan with 100,000 people which lies in the very center of the earthquake. Further news can be found in New York Times:

Report from New York Times

or Economist:
Report from Economist

Fig.4 wounded people receive the treatments in the street

After earthquake, many desperate parents are searching for their sons or daughters; Many children are crying for their missing parents; Thousands of people are still buried in the ruins of collapsed building while some are luckily being rescued by the arriving soldiers. Everywhere hospitals are full of the wounded, and medical cares are far less adequate to meet the need. It is now raining and cold in early May in Sichuan. Millions of people are still sleeping outside. And tents, blankets or sleep bags are all badly needed. Anybody who is willing to help can go to American Red Cross

or:

HongKong Red Cross
(Because China Red Cross is in Chinese)

Fig.5 A boy being rescued

Fig.6 A girl was pulled out of Collapsed campus buildling

Fig. 7 Thousands of people living outside after the earthquake

Fig. 7 Parents and grandparents are crying for their perished child

Fig. 8 The parents of a child killed in the school collapse. The child’s body is covered with cloth

Fig. 8 A student aiding a classmate still trapped in the ruins of a high school

Fig. 9 The rescuers are helping a trapped girl out of the ruins

Fig. 10 A injured girl is receiving treatment in the open hospital

Fig. 11 A nurse keeps on talking with a boy trapped in the ruin

Fig. 12 A wounded girl and her grieved grandma

Fig. 13 Survivors walking along a damaged road

Fig. 14 A doctor is encouraging a patient

God bless West China. God bless those people who are suffering from this terrible earthquake.

The second law of thermodynamics is ubiquitous, which can explain many phenomena from the ink diffusion in the water and the heat conduction from the hot to the cold etc. Or simply put, order is always decreasing in nature. Even an ancient Chinese philosopher, Laozi once said “ It is the nature’s law nature’s law to decreases those who have more than they need and increases those who need more than they have. it is not so with man. Man decreases those who need more than they have and increases those who have more than they need”. It seemed that nature always destroys the order and evens out everything in the world. Then how could life maintain its order? Why life is so unique? What are the differences between the matters with life and without? Order is important for life because losing order of life means that the atoms made of life will mix up with others in the universe. It is nothing but death.

The question can be best answered by an experiment given in Nelson’s classic book “Biological physics”. We have a glass tube with two freely sliding pistons and a membrane which only allow the water molecules to pass. It is full of water between two pistons. If we put some sugar in the right chamber of the tube, what will happen?

At beginning nothing happens except that we see the sugar gradually melts in the water and disappears. Then something strange happens: a mysterious force will slowly push the pistons to the right. If we put some small weight on the left end, it will left up the weight. i.e. it can do work. It seemed that we get some work done from nowhere.

However, when we look more closely, we found that the sugar only occupies half of space at the beginning and gradually it occupies the whole space as water flows through the membrane. The system loses its order and absorbs the heat in the air to do honest mechanical work. It is called the entropy force, which is actually the molecular driving force existed everywhere in the cell. This is one of the most important forces which underpin every form of life on earth.

Interestingly, the whole system can be turned around. If we put a heavy weight on the left side at the end of last experiment, the pistons will move to the left and the water will flow back to the left side as well, the sugar concentration will be higher and higher, and the whole system will gain order again. Here the mechanical energy is changed to be heat which dissipated into air around the tube. So if there is an energy flow from the higher order (mechanical one) to the lower order (heat), the system can gain order through the energy flow.

Aha, there we are. Life is NOT against the second law of thermodynamics. Neither is it an entropy-decreasing process which is defined by somebody as the essential feature of life. If we put the life and its environment together, the total entropy is still increasing. When we eat the food, the higher order chemical energy is changed to be lower order heat (Some are stored in the universal energy currency of life – ATP and they finally will be changed to be heat as well), we human being maintain our order of life

Life goes beyond the second law of thermodynamics

However, the story does not end here. If so, our life is just a biological car in a molecular sense, which could burn the fuel and do some useful work. Then life is mechanical and boring. The good news is, far from that, life is much more fascinating. For example, no matter how expensive gasoline you fill into your car, your Volkswagen will never be automatically changed to a Merced-Benz. There is no mechanical system can intrinsically increase its order and gain its complexity (Crystal can grow to be very large. But its periodic structure is simple). If we look at the history of life, which evolved from a single-cell organism, to multi-cell ones; from invertebrates to vertebrates, from fish, birds to primates and finally to human beings. Life not only maintains its order, it increases its order and complexity dramatically in the past 4 billion years. If we look back what leads us to the second the law of thermodynamics, we find that we couldn’t explain why only a rock hits the mud and the mud gets warm, but we never find that the mud pops up the rock and gets colder afterwards even it perfectly agrees with the energy conservation principle. Here we have a perfect parallel case: if we put the environment and life together, we only see that heat (or lower order energy) increases while life evolves to the higher order and complexity; we never see that the higher order energy in the environment increases while life degenerates and lose its order and mix up with the world totally, even it also agrees with the second the law of thermodynamics totally.

Maybe this could be a new law of life, which is predicted by Schrodinger:
“Living matter, while not eluding the ‘laws of physics’ as established up to date, is likely to involve ‘other laws of physics’ hitherto unknown……. from all we have learnt about the structure of living matter, we must be prepared to find it working in a manner that cannot be reduced to the ordinary laws of physics. And that not on the ground that there is any ‘new force’ or what not, directing the behaviour of the single atoms within a living organism, but because the construction is different from anything we have yet tested in the physical laboratory. We must therefore not be discouraged by the difficulty of interpreting life by the ordinary laws of physics. For that is just what is to be expected from the knowledge we have gained of the structure of living matter. We must be prepared to find a new type of physical law prevailing in it.”

In conclusion, Schrodinger just pointed out that the new law will NOT be against Newton’s law, or law of Quantum Mechanics, or any other law of physics. Instead, it could be some new law due to the complex and unique structure of the form of life. The key word of the new law could be Evolution, Order and Complexity.

This is truly a difficult problem. There are some intensive research in this field:

1) System study of the dynamic of an adaptive complex system. There are already some examples which show the order of a network can grow if certain rules are set. I would like write some articles about it later.

2) Chaotic and non-linear many-body dynamics. How to generate order from a chaotic system? Is there some universal rule to cause phase transition in chaos?

3) Mathematical Evolution theory and the mechanism to explain the order accumulation in nature.

They could lead us to some answers as well as they could be totally wrong. That’s the reason why research is so fun. Physics does not see the beginning of its end; instead, it is just the end of the beginning.

Recently Professor Jean-Marie Lehn gave an interesting talk about his perspective of Chemistry.

He is a French chemist. He received the Nobel Prize together with Donald Cram and Charles Pedersen in 1987 for his work in Chemistry. In 1968, he achieved the synthesis of cage-like molecules, comprising a cavity inside which another molecule could be lodged. Organic chemistry enabled him to engineer cages with the desired shape, thus only allowing a certain type of molecule to lodge itself in the cage. This was the premise for an entire new field in chemistry, sensors. Such mechanisms also play a great role in molecular biology. (From Wiki http://en.wikipedia.org/wiki/Jean-Marie_Lehn)

Fig. 1 New molecule which he synthesized

I went to his talk because that he was not only talking about chemistry, he would talk about the principles of building molecular machines with well-defined structures. In his speech, he described a chemical system composed with many small reusable parts can undergo continuous composition, decomposition, recombination or reorganization to reach a design state by responding to temperature or magnetic field etc. Simply put, he painted a blueprint of a chemical system with parts which can self-evolve like something with life.

He told us that his inspiration comes from observing the phenomena in the life world. Nucleotides can self-organize themselves to form DNA, microtublins can form microtubules and can also be decomposed into parts and be reused later; virus can use simple proteins to form its walls. With this idea in mind, he showed us that by using Cu ions and some polymers a double helix or even triple helix could be formed by the self-organization. He also used the similar materials to form a regular 2D or3D rectangular grid. With these building blocking, in theory you can build many well-defined and functioning molecular structures with different geometry and different size. This offers a powerful alternative for Nano-fabrication and Nano-manipulation. Because you don’t need a super-tiny tool ( either laser or other chemical reactions) to curve materials into certain shapes. You can synthesize them in the first hand, instead.

These supermolecular structures are just like bricks: you can use bricks to build a functioning structure and then you can break it and build it into other shape again. With this idea in mind, he further develop it into a wonderful new idea: rather than design ONE molecule with certain functions; we can create millions of these suprmolecular structures and build a selection function to choose the right ONE which we need. Traditionally the molecule design is like make a key for a lock. You have to understand lots of information about the lock and make a right key for it. Now you wouldn’t bother. You simply create a mechanism to create millions of different keys ( they can be built from simple and repeatable parts), and let the lock be the selection to choose the right key. If the key fits the lock, it is OK; Otherwise the decomposition and recombination process will go on.

This really brings a revolution idea to the drug design process. Now the widely-used strategy is: after we find a target molecule for certain disease, we will use all known chemical molecules in the molecule library and screen them one by one to see which one can bind to the target molecule. Then these molecules are synthesized, tested on mice, then tested on human beings. The whole process is not efficient and cost lots of time. With this supermolecular structures, the target molecule can choose the right molecules to be the potential drugs. Also you don’t need a whole molecule library, you only need some reliable and reversible molecular building blocks to do this job.

Finally he mentioned a more challenging idea: adaptive evolution chemistry. Dynamic chemistry is no longer just about dynamic chemical reaction theories, not even motional chemistry which will address molecular motion and shape changes. It will finally become constitional dynamic chemistry, which will build theoretic foundations of modification of chemical entities and how to re-build them.

“This may be not new at all. There may be a chemical evolution well before the biological evolution. There must be a long way for simple inorganic molecules to form some basic units of life, some molecules can store energy, some can store information and some can self-copy themselves. One day, we may have Darwinian chemistry to address these problems.” He finished his speech with a smile.

The 5th European Conference on Complex System was holding in Dresden, Germany. This is really an emerging research area. The multiple parallel sessions themselves show how diverse and multi-disciplined it is. It includes:

• Complex system method
• Brain and Cognition
• Networks
• Social system
• Biological system
  Researchers not only from all countries of Europe, but also from US, Canada, Japan etc. Unfortunately, there are few Chinese researchers. The most inspiring experience of this conference is that the traditional barriers among disciplines are broken down. You can hear the hybrid system of brain tissue and microelectronic chips, systems biology illustrated using the virtual heart, then mathematical model of rhythmic behavior in biological system, and a speaker from HP computer Lab talked about social dynamics in cyberspace, mentioning the network properties and quality control of Wikipedia etc.

Today’s most heated topic is Prof. Denis Nobel’s talk about his revolutionary views about system biology. When I talked with several participates after his speech, they were all quite impressed. He called his 10 years research experience in the field as ten commandments in systems biology.

Commandment 1 (C1): Gene itself has no functions.
It is actually the cooperation and system of genes lead to the function of living things.

C2: Transmission of information is NOT one-way
Traditionally we think that gene decide protein > pathway > sub-cellular > cell>tissue-> organ->body. He thought that it is totally wrong to start from gene, proteins and then build everything. It is doomed to fail. Gene expression is also decided by the cell culture and proteins to translate them.

There is no magic gene/ genes to cause Cancer, homosexuality, selfishness or high blood pressure. All functions and malfunctions of human being in all level are system properties emerging from the network and interaction of elements.

C3: DNA is not sole transmitter of inheritance
It is quite anti-Darwinism and pro-Lamarkism. But there are some scientific evidences for that. More can be seen in article:

Jane Qiu (2006), “Unfinished symphony”, Nature, 441, 143-145

C4: Theory of biology Relativity
We need to understand the interactions at all level to understand the real functions of living things. We can not unlock nature’s myth only from bottom-up strategy. That is, we can not understand the organism only from gene level up to cell level etc. We have to understand it from organ regulation on the cells or genes.

C5: Gene ontology will fail without high-level insight
It is very misleading to find the causes of cancer from the selection of genes without clear understanding the physiology of cancer and evolution theory of organs. Gene is called a blueprint of life. It is wrong. Gene is NOT the book of life. If it is the book, it is the book with huge gap which can not be read at all.

C6: There is not “genetic program”
Gene itself is not a program of life; it is only the database of life. There is NO program written in the gene. The reading of this database comes from the cells and the proteins to transcript and to translate them.

C7: There is no program at any other level
Life is like a well-coordinated concert but without conductor. Further reading
“The art of Gene”, Enrico Coen ( Oxford Univ Press, 1999)

C8: No program from any level, including brain
Life is an emerging property of a complex system of the interactions of proteins and cells

C9: Life is the self integrated process, not an object or substance.

C10: There are many more to be discovered, the theories of biology do NOT yet exist. Seeking theory/ies is real challenge in system biology.

(Denis Biography from Wiki)

Denis Noble (born November 16, 1936) is an eminent British biologist who held the Bourdon Sanderson Chair of Cardiovascular Psychology at Oxford University from 1984-2004 and is now Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of Systems Biology and developed the first viable mathematical model of the working heart in 1960. His research focuses on using computer models of biological organs and organ systems to interpret function from the molecular level to the whole organism. Together with international collaborators, his team has used supercomputers to create the first virtual organ, the virtual heart.

Noble was educated at Emanuel School and University College London (UCL). In 1958 he began his investigations into the mechanisms of heartbeat. This led to two seminal papers in Nature in 1960 giving the first proper simulation of the heart. From this work it became clear that there was not a single oscillator which controlled heartbeat, but rather this was an emergent property of the feedback loops in the various channels.

When I came to the institute, my collaborator Kay invited me for a dinner in the new town together with his friend Thilo and other guys. The city is wisely divided into two functioning areas, old town and new town. All the ancient buildings like King’s summer palace, women’s church and opera house are in the old town; while the restaurants, bars and other modern buildings are in the new town. Each is in harmony with its environment and cultural atmosphere. We went to an Italian restaurant. The sentence on its menu board reads: ”think globally, eat locally”, which roughly means that even it is a local restaurant, it offers global food options. It is true. After ordering the food, it turns out that six of us ordered totally different food: Kay ordered American style fish salad with chips, Thilo ordered Greece style salad with bread, Martin ordered beef steak cooked in North European way, I ordered Chinese style fried beef and vegetable with rice. It was still summer then. We sit around a long table under the shade of the vine in the backyard of the house. It was green everywhere, with green plants covering the wall, lovely flowers blooming in the small Garden. There was a well for fetching water, just like any ordinary local residence here. Several big candles were burning since it is getting dark. A man in the casual dress was playing his guitar and singing lovely Italian songs.

After the dinner, with beers in hands, Thilo began to tell his stories when he once was a researcher in the math department of Princeton University. He said, academic jobs in the university are quite demanding. You have to play a multiple roles in one person, as a researcher at first hand, also as a lecturer to teach courses for undergraduates and postgraduates; a fund raiser to get money for your research group; a manager to handle with quite a few Postdocs and Phds in your group; a faculty member for the service in the department; a paper reviewer or an editor for your academic community. You don’t need to be smart to know how busy an academia is. “publish or perish”, the cliche still works now days. Without enough papers published, without enough founding, you will fail before this strict rule, “up or out” , if you don’t get your tenure within six years.
“ Then how those big names do their research?”, somebody asked.
“ Today I will reveal a secret”, he paused.
“ What secret? Don’t be mean, please tell us”, we said.
“ OK. Do you guys know Fermat’s Last Theorem?”
“ Yes, we do”
“ Do you know who proved this theorem?”
“ Aha, you call it secret? Everyone here knows that is it is Prof. Andrew Wiles who spent about 10 years to prove it. The final proof from him came in publication in 1994”
“ It is correct. However, do you guys know how Prof. Andrew Wiles found these 10 years to dedicate himself to the Great Fermat theorem?”, he signed, “Prof. Andrew Wiles told me by himself, in order to focus on the proof of the Fermat’s Last Theorem, there was one year in which he worked extremely hard to write 20 papers and locked them up in his desk drawer. Then he would pick up two to publish each year. In this way, he gained precious ten years to allow himself to do nothing else except Fermat’s Last Theorem”

Nobody spoke anything for a while. Everybody was pondering on something. Now days in the era of science research being measured by SCI, Impact Factors, funding committees etc., most researchers would not risk themselves to focus on some true problems which demand some deep insights and long commitments. This is a simple fact in our current funding system. No wonder, in a report to the US president by President’s Information Technology Advisory Committee, named as “Computational Science: Ensuring America’s Competitiveness”, a group of leading scientists expressed their concerns:

“Based on its analysis of Federal R&D agency activities, PITAC concluded that Federal support for computational science research has been overly focused on short-term, low-risk activities. In the long term, this is actually a high-risk strategy that is less likely to yield the high-payoff, strategic innovations needed for the future.”

Now we are in the age of competition: everything is required to be done faster; everybody is required to produce more with less time. Nobody knows what the end of this road is; Nobody knows whether it is the right way. It is more or less to make people to feel nostalgia about the golden days of science in the past time, before NSF or any other funding committees are established. For example, in Cambridge University, after becoming a member of the faculty, you have the freedom to do whatever you like to do within the university’s resources. You don’t need apply any special funding for it. Nobody will evaluate your research every 2~3 years. However, those golden time is gone. Now we can not undo what we had already done. More importantly, we can not back to the age of doing science without complicated devices and giant machines, which are essential for the progress of bio-science and nano-technologies etc.

What could we do? It is impossible to ask researchers to work harder, like Prof. Whils did his pre-work before the proof of the Fermat’s Last Theorem. Some young researchers have already died prematurely for their overworking, such as in Dr. He Yong in Zhejiang University. We also could not change the system of competitive application for funding and the peer-review, which have been proved to be the pillars for the current progress of science. Maybe there is NO solution for everybody in general. Each one has to create your own means to meet your own ends. Just like what Prof. Wiles did, we should know what our real interest is and hold it dear to our heart always, and then try to do the best from the least.

Whenever I read the Steve Jobs’ commencement address in Stanford, I could not help being moved by his “three stories”, which are linked together to make his life shine like a diamond. He is a real man, a true hero who sticks to his ideals always. At the end his speech, he said:
“When I was young, there was an amazing publication called The Whole Earth Catalog, which was one of the bibles of my generation. It was created by a fellow named Stewart Brand not far from here in Menlo Park, and he brought it to life with his poetic touch. This was in the late 1960’s, before personal computers and desktop publishing, so it was all made with typewriters, scissors, and polaroid cameras. It was sort of like Google in paperback form, 35 years before Google came along: it was idealistic, and overflowing with neat tools and great notions.
Stewart and his team put out several issues of The Whole Earth Catalog, and then when it had run its course, they put out a final issue. It was the mid-1970s, and I was your age. On the back cover of their final issue was a photograph of an early morning country road, the kind you might find yourself hitchhiking on if you were so adventurous. Beneath it were the words: “Stay Hungry. Stay Foolish.” It was their farewell message as they signed off. Stay Hungry. Stay Foolish. And I have always wished that for myself. And now, as you graduate to begin anew, I wish that for you.

Stay Hungry. Stay Foolish. ”

I am Joseph Zhou, a researcher of biophysics in the department of Biological Physics of Max Planck Institute for the Physics of Complex Systems, Germany. I am interested in the molecule dynamics of proteins and protein-protein interactions networks, the regulation and signal network of the cell, and signal amplification in the cell during the mitosis.

My current research involves finding the relationship between protein dynamics and drug resistance of the HIV protease. Instead of using a traditional measure of “genetic distance”, a dynamics-based measure is used to build a phylogenic tree of HIV-1 protease. The relationship between the mutation and the drug-resistance can be revealed by the analysis of the tree. Traditional dynamic analysis for biomolecules is complicated and time-consuming. My colleagues and I are trying to employ a smarter method to investigate the changes of the protein dynamics due to the sequence mutations of HIV protease. Our results so far show that the mutations have obvious effects on the movements of the “flaps” of the HIV protease. The relationship between the change in dynamics and the drug resistance can be clarified from our further analysis of the genetic homology.

I do believe what Denis Nobel said about the approach about biology (you can find my former blog about “Ten Commandments in system biology” http://www.imechanica.org/node/2050). The life can not be worked out simply from the bottom-up approach. Gene is just the music score of the life. There is a mysterious mechanism in the cell, tissue even organ level which reads the score and play the music of the life. So the main topics of my blog will cover:

1) Report my research on the collective effects or emerging properties from the network of genes, proteins and cells; Hopefully, I could find some researchers who share my interests and we can discuss or even collaborate :-)

2) Comments and introduction on the new ideas from the conferences, seminars, workshops which I participate.

3) Other interesting topics about biophysics, cell development, tissue growth, network etc.

On the personal side, I am quite a fan of Classic music, from Mozart, Schubert, Chopin, Debussy, Scarlatti…, you name it. :-) However, I also like folk singing and I have a large collection of the albums of folk songs across Europe. One of my favorite group is MadriGirls. They sing songs with a special interests in early music. You can listen to their wonderful voices in their website in mySpace: http://www.myspace.com/madrigirls.