Dear members of ION: Happy New Year to all!

This is the beginning of the sixth year of ION’s existence, and I am happy to say that we are well on our way to reach our goal of becoming a world-class institution by 2010. A stream of first-rate scientists are joining ION to head new laboratories, and our students are doing excellent laboratory work with a high spirit, two of our PIs have been invited to speak in important international meetings, more high-quality papers are in the pipeline to be published, and ION is gaining a reputation around the world as a notable scientific institution in biological sciences in China. However, despite all these hopeful signs, I would not be frank to you if I did not express my deep frustration over the past year as the Director of ION. What I am about to say may sound depressing and discouraging, but I hope everyone can share my feelings, and help me and ION to face the difficult time ahead.

First, I want to inform you that ION is in financial trouble. With our continuing success in recruitment and the demand for start-up funds, we have not only depleted all our resources, but also in debt of more than 10 million RMB by the end of 2004. It has been one of the founding principles of ION that we will not ask for extra resources from the government unless I am convinced that it is necessary for us to carry out high-quality research. The reason is simple: ION is not a successful example of Chinese institution if it is built by an excessive amount of resources that is unlikely to be available to most Chinese institutions.

This financial difficulty may not be too worrisome if it were not for the fact that the big weather in the Chinese scientific establishment has turned steadily against our goal of achieving high-quality basic research. Strong wind is blowing in and out of CAS against our approach in doing science – the small laboratory, individual scientist-based fundamental research, which on the surface appears to be driven by the desire of publishing papers in high profile journals for our personal glory. The ION and myself have been directly or indirectly criticized for not being able to put up “big banners” for pursuing organized projects aiming at disease-oriented, socially-relevant research. Even a few million RMB a year of director’s fund originally promised by CAS (the only money that was additional beyond the regular CAS support to its institutes) has stopped coming, while tens to hundreds of millions are channeled into other new and old institutes and into big projects organized by administrators or researchers who can put up attractive banners with abstract or superficial aims. To my mind, there is no future for Chinese science if a small institute like ION with such a minimal demand for resources and having achieved the best record of high quality publications in neuroscience in China, is suffocated by the drive for “big science”. (See the article enclosed)

I am also frustrated from within ION. I see some of our PIs and students spending their research money and wasting resource of ION without second thoughts. Projects are initiated and large purchase orders were made without careful thinking. Unreasonable amount of research money (by any standard in the world) was spent by some PIs on entertainment and travels, some of which are clearly for personal reasons and for leisure. Most of our laboratories are well-off at this time, some with millions in reserve funds, because ION offered generous start-up funds and I have put all ION resources into our laboratories, by giving each lab a higher level of operating funds than other institutes and by reducing the charges for lab facilities and core equipment use at a level way below the standard rates.

I am frustrated at an even deeper level as a scientist with some social conscience. I am deeply troubled by the fact that many of our young students and PIs appear to put their self interests at such a high level, with little regard of the common good of our institute and our society at large. The cost of a poorly thoughtout research project or a poorly used equipment may suffice to support the livelihood of an entire village struggling to survive, as I have seen with my own eyes in the poor Gueizhou and Ningxia countryside not too long ago. To many scientists now competing for China’s limited research money, resources appear to be there up for grab (“bu na bai bu na”) and everyone is for him/herself. Personal greed is now well-justified within our scientific circles by glorified dressing of scientific pursuit. Gone is the time when sacrifice for others and simply “service for the people” is considered to be a virtue.

I am not a person with the desire to be a saint, nor do I believe that everyone should strive to be a martyr. However, I do put common good at a higher priority, sometimes above my own interest, simply because I consider myself to be very lucky, well-rewarded by the society, thus obligated to yield my contribution. Most of our students are privileged and well-nurtured by our society. I am saddened to see the lack of concerns for common good among many of them, as reflected in how our common resources are used at ION (including toilet papers). What our students are concerned about, as reflected by BBS postings, seem to be mostly immediate personal matters, glory of personal success, with endless gossips and cynicism. Where is the precious idealism that characterizes the youth? Where is the zeal for scientific pursuit or social involvement that we may see in budding scientists of our future? Of course, ION is but a part of the society. But, but can we at least build a small community and an environment that we can all be proud of and years later remember it as a place where people are inspired and driven by ideals?

These may all sound too depressing for the start of a new year. If my new year messages are but a record of personal reflections as I struggle through the growth of ION, I hope that I will find this message silly and unnecessary when I retire from ION as the director. I have recently overheard the comment of an ION student that ION is my “baby”. It is probably true. As such, I do hope you forgive my parental complaints and incessant demands.

Mu-ming

P.S. Enclosed is an article commissioned by Nature for “Nature China Voices II”, in which I elaborate my view on how science should be done in China at this time.


Big Science, Small Science

Mu-ming Poo

When I began my graduate study more than thirty years ago, my first exposure to scientific research was in a big high-energy experimental physics laboratory, where I helped to assemble a particle detector made of precisely aligned gold wires. After the detector was made, it was shipped to another university for testing, and eventually ended up as part of a big machine in Geneva. As a lowest ranking participant in a project that involved hundreds of scientists, I was not informed about the details of the project and had very little idea about the bigger picture. I later left the laboratory in part because of the alienation with the scientific problem I was supposed to be studying and the feeling of “a small cog in a big machine”. I eventually completed my first piece of work in a biophysics laboratory, where my supervisor and I could ask a question, perform the experiment, and receive an answer in a matter of days. In retrospect, my interest and motivation in science were probably consolidated and sustained over the years by the pleasure of finding things out myself in my own laboratory, confirming or refuting my own hypotheses on how things work. Of course, personal credit and recognition I received from my peers for a few discoveries I have made must have contributed to my enjoyment of scientific life. Like most scientists of my generation, I grew up in a small laboratory and made my contribution to science in a way that is now referred to as the “Small Science”.

Winds are blowing in the West and East for “Big Science”, and large amounts of research funding are channeled into genomics, proteomics, or “x-omic” projects. In China, Big Science fits well with the existing top-down approach of scientific planning and organization, and is perceived by some decision makers as the future trend of science. Many scientists are busy writing grand-scale proposals, typified by projects costing on the order of 0.1 to 1 billion US dollars.

Should a developing country put major emphasis on Big Science? This is a question particularly relevant to China at present when ambitious long-range plans for science and technology are on the drawing board. Here I discuss the pros and cons of Big Science vs. Small Science, within the context of life sciences, although these comments may apply to other natural sciences as well.

Science Big and Small

“Big Science” is here defined as projects organized by a small number of political or scientific leaders in a “top-down” manner. It requires a huge sum of money and the participation of many laboratories and scientists in a coordinated manner. In China, projects organized by the Ministry of Science and Technology (MOST) or other government agencies, such as the 12-year plan in 1956, “863” & “973” projects, and the megaprojects associated with the current Mid-to-Long Term National Plan for Science and Technology, fall into this category.

In contrast, “Small Science” projects are those initiated by individual scientists, funded by much smaller research grants through competitive peer reviews, and carried out by a single or a small number of laboratories. Research projects funded by National Natural Science Foundation of China (NNSFC) are examples of Small Science. In China, Big Science operates in a way similar to the “planned economy”, whereas Small Science is more analogous to “market economy”.

Big Science entered modern scientific scene first in high energy experimental physics and astronomy, when the amount of resources and the difficulty of the tasks demanded the involvement of a large number of scientists working under a well-orchestrated scientific management. In 1971, the Nixon administration proposed a big bioscience project called “War against Cancer”, aiming to cure cancer by 1976. More than three decades have passed, cancer remains one of the most devastating diseases. We now realized that cancer is a complex biological problem that cannot be solved by a big project with a fixed deadline, regardless the amount of resources devoted to it. Substantial progress has indeed been made in the cancer field in the past three decades, but it was due largely to discoveries made by individual researcher-initiated small projects.

Human Genome Project is another example, and it turned out to be a huge success. Unlike the “War against Cancer”, it was technology-based and has a clearly-defined and measurable goal - sequencing the entire human genome - a goal that is achievable even with low-tech sequencing techniques, although not as efficiently. The end product of the genome project is not as much in the scientific insight as in the new information that may facilitate scientific pursuits by individual laboratories. The enormous amount of new genomic information gained by this project has changed the way biology and biomedical research is done in many laboratories, and has provided a basis for new biotechnologies and new disciplines of bioinformatics and “systems biology”.

A successful big science project has the following features: First, it has a well-defined target. Second, it is initiated by scientists themselves and receives enthusiastic support by the scientific community at large. Third, the timing for the project is ripe and the particular scientific field is ready for it. A big science project that deserves the support by the government should go through a rigorous process of formation and evaluation by scientists themselves, besides its appeals to the government.

Why small?

The success of Human Genome Project has created a perception among many scientists and policy makers that future progress in life sciences will mainly come from big projects with grand-scale attacks on biological problems. Some believe that the era for small science is gone and hypothesis-driven research is over – just get all the information by high-throughput methods, the pieces will fall into their proper places and the puzzles will be solved. It is argued that all we need now is to have more and better machines that can yield the complete set of x-omic information, more technicians to run the machines, and more “bioinformaticists” to analyze the information, we will then understand all there is to know about how biology works, how diseases originate, and how to cure them.

However, history has taught us that major breakthroughs in science, particularly those in life sciences, were mostly made by individual investigator-based small science. In biology, ground-breaking discoveries such as the double helical structure of DNA, the genetic code, the oncogenes, genetic control of development, programmed cell death, and mechanisms of learning and memory – to name a few – were all made by individual scientists through small laboratory-based research. In the field of biotechnology, major technological advances – recombinant DNA, monoclonal antibody, molecular cloning, polymerase chain reaction (PCR), and stem cell technology – were also without exception made by small science research. This is unlikely to change in the coming decades.

Scientific advance is unpredictable and requires exploratory efforts by a large number of small laboratories, each using different approaches. While visionary scientists may have a sense of the general trend of science, it is difficult to predict in which area the breakthrough will come, and when. The small laboratory setting is also more effective for interaction among scientists, for inspiring creative ideas, for performing innovative experiments, and for solving intellectually and technically difficult problems. Furthermore, motivation that drive many scientists in their work – personal interest in a particular subject, competition with their peers, and individual recognition by the scientific community – diminishes when the work involve a large group of scientists.

Most importantly, small laboratory setting is more suitable for training of young scientists and for establishing mentor-apprentice relationship, in which the lab supervisor directly interacts with lab members and is fully aware of the experimental design, data analysis, and the interpretation of results. Students learn “the art of soluble” (to quote Peter Medawar) directly from the mentor through personal interaction. This interaction involves not only learning practical skills in solving problems at hand, but also acquiring through permeation the aspiration in science, the curiosity about nature, the style and taste in research, and the personal integrity when judgments on scientific or non-scientific matters are called for. Such master-apprentice relationship has yielded generations of great scientists of the twentieth century.

In short, small science laboratories are the place where important works are being done, and is the best training ground for the next generation of scientists. More resources should be channeled into small laboratories and used for cultivating a new generation of scientists who are not only interested in pursuing science, but also trained to ask the right questions and design the right experiments, in order to sort out the relevant information from a large amount of noise generated in the new informational age.

Perils of Big Science

The recent hype in China for big life science projects has raised serious concern among many Chinese scientists. National pride may have driven the government and science administrators to go for big science projects prematurely. Big projects are intrinsically risky. They call for careful planning and proper assessment of the availability of well-qualified researchers in a given area. It will have a serious negative impact on the scientific community by diverting major resources away from small research projects, where resources are already very limited. There is also serious concern on how big science proposals are formulated and evaluated, and once the project is funded, how it will be monitored.

Proponents for big science projects often argue the usefulness of research and development of large-scale, sophisticated technologies, e.g., high-throughput DNA sequencing or chemical screening facilities, “platforms” for genomic, proteomic, and bioinformatic analyses. The development of cutting-edge new technologies requires a strong base of basic science laboratories, which is yet to be established in China, huge funding associated with big project is most likely to be used for importing current existing technologies. Acquisition of existing advanced technologies is not justifiable unless there is already a sufficient number of active laboratories that can use the technologies effectively.

One may argue that channeling the interests and organizing the efforts of a group of small laboratories into a big project aiming at a common goal, e.g., the cure of hepatitis or Alzheimer’s disease, is a reasonable strategy. Under the condition of limited resources and shortage of high-quality researchers in China, scientific research may need to be a more organized endeavor directed towards societal needs. However, unless genuine interest can be raised among the scientists working on designated tasks within a big project, organized efforts based on financial incentives usually do not function well.

In fact, participation in earlier big projects such as “863” and “973” was generally viewed by Chinese scientists as a means of securing large amount of funding without serious peer review. Many of these big projects had very little impact on the research direction or the productivity of the participating laboratories. While some progress had been made by a few leading laboratories, large amounts of resources were channeled into mediocre laboratories, which were packaged into the project through institutional and personal connections.

Finally, a simple financial consideration will be illuminating. The current annual budget of NNSFC is about 2 billion RMB, of which one-fifth is devoted to life sciences, while a large science project currently under consideration is 10 billion RMB. Even if the latter funding is distributed over 15 years, it is still larger than the entire annual NNSFC budget for life sciences. Putting major resource into grand-scale science projects in China at this time simply does not make sense, in view of its current total budget designated for natural sciences.

Basic Science, Applied Science and Technology

There is a prevailing attitude among policy makers and administrators to consider science and technology (“Keji”) as one thing; science projects are no different from engineering projects, and are planned and organized in the same manner. Take an example in biomedical sciences, projects aiming at conquering diseases are viewed as projects that can be achieved simply by mobilizing scientists into well-planned strategies in solving the problems directly related to the disease. However, there are distinctive differences between understanding the normal and disease processes (science) and developing treatments for diseases (technology).

Breakthroughs in our understanding of the biology of the disease process, which forms the basis for developing treatments for the disease, will come only when a large number of capable researchers, each driven to work on a basic biological problem of his/her own interest and to provide a definitive solution to the problem. Important breakthroughs usually come when scientists have put their entire hearts and minds into the project, not by the usual half-hearted participation in an organized project lured by available funding.

Although an application of existing technology may be initiated successfully by top-down planning, development of cutting-edge new technology is as unpredictable as basic sciences. Like scientific discoveries, major technological breakthroughs often arise when talented individuals are driven to work by their own interests, solving their problems in ways that cannot be predicted.

While China has made significant improvements in the quality of research in life sciences, there is still a serious lack of well-trained researchers. Organizing big projects without a sufficient number of high-quality researchers with a track record of significant productivity will undoubtedly lead to the waste of resources. Thus for basic sciences, including life sciences, a more appropriate strategy is to disperse the funding into small projects, with strong emphasis in supporting research of high quality and originality. Only through high quality research can we expect scientific progress of true significance to both basic science and technological applications.

Max Perutz had once remarked that “creativity in science cannot be organized, and hierarchical organization can kill it”. Scientific development depends on government funding, but research progress and direction cannot be planned, a fact best exemplified by Perutz himself, who founded and led the Laboratory of Molecular Biology in Cambridge, in which twelve Nobel laureates emerged with discoveries that helped to lay the foundation of modern molecular biology and much of the current biotech industry.

Strengthening Basic Science

It is a glaring and mystifying fact that in the current Mid-to-Long Term National Planning for Science and Technology, only one of the twenty designated subgroups concerns basic science. This directly reflects the low priority basic science is placed by the government. Some top-level advisors to the government had purportedly argued that since China is so much behind the West in basic science and it is difficult to improve the productivity in this area, it is economically sound to put basic science into a minor role and focus the resources into applied science and technology relevant to the current societal needs. After all, fruits of basic science can be shared around the world.

This view is short-sighted and misleading. The major limiting factor in China for future technological advances in all fields is its weakness in basic science, especially in the field of biomedical research and biotechnology. In an age that increasingly values original contributions and intellectual properties, sharing scientific fruits with advanced countries will be costly and inefficient, unless one is content with leftovers. Furthermore, as China marches towards a relatively affluent (“xiao kung”) society, science must be viewed beyond its utilitarian value – as merely subservient to technology and social welfare. Basic research is the root of scientific culture that forms the foundation of a modern society, a culture that values intellectual endeavor and rational pursuit of objective truth for its own sake. For the scientific culture to take roots and to bear fruits, basic science research provides the rich soil and small science laboratories provide the ideal environment.