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“It suddenly struck me that that tiny pea, pretty and blue, was the Earth. I put up my thumb and shut one eye, and my thumb blotted out the planet Earth. I didn't feel like a giant. I felt very, very small.” – Neil Armstrong (1930-2012)

Fresh Reads from the Science 'o sphere!

Thursday, February 22, 2007

Wild Biopolis

Although the Biopolis appears to be a highly sterile environment on the inside, there is an interesting assortment of animals that live in its gardens or around the premises.

Here are some animals that I spotted in the past year:

This tiny crab spider tried to hitch a ride on my shoulder into the lab. I managed to trap it in a Milo paper cup to take a closer look. A fellow graduate student who had a camera with a macro function took this photo for me. Later I released it back into the gardens.

Here is a fairly large grasshopper with orange legs. I've never seen grasshoppers with orange legs before. I also like the yellow grid pattern on its back.

This is an even larger grasshopper with glassy eyes. It must have been injured because it was hobbling around on only one hindleg. Its right hindleg is missing.

I spotted this black moth flying around from quite some distance away. Luckily for me it took a rest on a low-lying leaf and gave me a chance to take a photo of it. It has a nice blue-white halo pattern with some damage on its left wing. I'm not sure that it's a moth, I only assume it is not a butterfly since it spreads its wings open when resting.

I love egrets. They have beautiful, long wingspans and fly so elegantly. Unlike smaller birds like swallows which have to flutter their wings like mad in order to stay in the air, egrets flap their wings slowly and gracefully. Their landing approach resemble that of an aeroplane, gliding in slow with wings fully outstretched.

Here is one (I think a common egret) that landed on a grass patch near Biopolis. It had a few other companions. Since egrets are migratory birds one can only guess how far away their eventual destination was.

Sometimes after the rain you can hear toads croaking in a grassfield, but I didn't catch this one by sound. I was walking home one night and this toad hopped out of my path into the safety of a grass patch. It then stayed very still and very quiet - it didn't even flinch when I fired the flash at it from a few centimetres away.

And finally this quick lizard was scurrying to safety towards a tree when I caught a shot of it. These lizards are quite common to the area. I wonder why it has a dark-coloured throat though, other lizards appear to have a lighter coloured throat.

Sunday, February 18, 2007

Repulsive Bugs

Every life science student knows the drill:

Eukaryotes = clever cells with membrane-bound organelles. Ah, such intricate elegance; did I mention the nucleus? The Golgi apparatus?

Prokaryotes = stupid bugs with no organelles. Their only job in the known universe is to make us sick and miserable.

Unfortunately Nature has a habit of not adhering to neat categories. Or more correctly, our neat categorizing.

In 1975, Richard Blakemore discovered a group of bacteria that respond to magnets. If you point the North pole of a magnet at them, they swim toward it.

No big deal, you say. Maybe the bacteria randomly swallowed up tiny pieces of iron and got attracted to the magnet.

Then, Prof. Blakemore turned the South pole of the magnet at the bacteria, and guess what?

They swam away.

Now that's odd. Ferrite particles should be attracted to either pole of a magnet. The bacteria didn't just contain ferrite, they contained magnetite.

In addition, even if they contained magnetite, the magnetic field should have flipped them around and attracted them anyway. So they didn't just react passively to a magnetic field - they were actively swimming away from the S-pole. This ability to move in response to a magnetic field is called magnetotaxis.

It gets even odder:

1. Magnetic bacteria don't simply eat random pieces of magnets floating around. They biosynthesize their own ferrite particles by absorbing Fe (III) ions from their environment, producing particles with very consistent size (50-100nm) and shape.

2. Somehow in the process of making these particles, they get magnetized.

3. They synthesize each magnetite particle inside one membrane-bound vesicle.

4. On top of that, the magnetosomes (vesicle + magnetite inside) are arranged in a neat chain. Chain formation is a highly organized and regulated process. In fact, the magnetosome chain is the most complex structure in a prokaryote cell.

So magnetotactic bacteria do have membrane-bound organelles. And because they are anaerobic, they die quickly in the presence of oxygen and don't cause much trouble for people.

Scientists hypothesize that these bacteria use their magnetosome chains to orientate them and allow them swim deeper into the soil, away from the dangerous oxygen-rich top layer.

These bizarre magnetic bacteria are not only a scientific curiosity, but because they can synthesize tiny, single-domain magnets of consistent size, they are also potentially useful industrial tools. Magnetosomes can be isolated by sonicating the bugs (breaking them open) and then centrifugated and purified.

This is what purified magnetosomes look like:

In addition, the magnetite particles are enclosed in a phospholipid membrane, which makes them biocompatible. Thus, they are suitable for a wide variety of biotech and medical applications.

During the 1970s and '80s, progress in this field was slow due to a number of technical reasons. Recently, the isolation of new strains and new techniques for handling these strains allowed significant progress to be made.

Prof. Dirk Schüler of the Magneto-Lab at the Max Planck Institute in Germany is a leading expert on one species of magnetotactic bacteria, the Magnetospirillum gryphiswaldense. He believes that current technology for magnetosome production has already reached industrial feasibility.

This means that we can expect to see some "attractive" applications for these bugs within the next few years!

Ha ha ha! That joke fell completely flat.

In fact it was rather repulsive.

Would you like to know more?

About magnetic bacteria
Magnetotactic Bacteria: you can download a Nature Reviews article on "Magnetosome Formation in Prokaryotes" here

About other bizarre organisms
Planarian worm

Wednesday, February 14, 2007

Let This Mistake Continue? Part III

Was it a mistake?

The analysis continues...

4. Is the pharmaceutical growth a result of the biomedical push?

From the official report by A*Star, the biomedical manufacturing increased an impressive 30.2% over 2005 to S$23 billion dollars. Most of the output came from pharmaceutical industries (91%) and employment increased by 3.9% to reach 10 571.

However, Prof. Lee pointed out that the output from the biomedical sector cannot all be attributed to the billions being poured into the research drive, because there was already pharmaceutical manufacturing predating the push.

She then said that "Singapore's biomedical research initiative is not an important consideration except in the few cases where pharmaceutical companies have joint research ventures with A*Star."

I think that it is good that Prof. Lee is clarifying the difference between biomedical research and manufacturing. To see if her views are true, I went to the websites of prominent pharmaceutical companies in Singapore to find out when they came here. I also read through this long list of speeches given by key government officials regarding important events in the biomedical sector.

Here are the results:

Pfizer = 1964 (very small office then)
GlaxoSmithKline = 1970s
Schering-Plough = 1995
Eli Lilly = 1996
Novartis = 1997 (Ciba Geigy since 1971)
Merck Sharp & Dohme = 1998

Since the Life Sciences as an economic direction was announced by Mr. Philip Yeo only in Sep 2000, you can see that Prof. Lee's first observation is correct. Many international pharmaceutical companies were already alive and well before Singapore's biomedical initiative. The current industrial growth is not the direct result of research discoveries here in Singapore.

However, these pharma companies have not only grown in production output, they have also invested new infrastructure and even R&D departments into Singapore.

Here is a list of pharma investments in Singapore (focusing only on the abovementioned six companies) after Mr. Yeo's speech:

MSD (Sep 2001) - Multipurpose Chemical Bulk Actives Manufacturing Facility
Eli Lilly (Nov 2002) - Lilly System Biology Centre
Novartis (Jan 2003) - Novartis Institute For Tropical Diseases
MSD (Oct 2003) - Pharmaceutical Formulation Facility
Schering-Plough (Dec 2003) - Multi-Product Bulk Pharmaceutical Plant and R&D Facility
GSK (Jun 2004) - GSK Expanded Facility
Pfizer (Jul 2004) - Multi-Purpose Manufacturing Facility
Novartis (Mar 2005) - Novartis Singapore Pharma Manufacturing
GSK (Nov 2005) - R&D Pilot Plant
GSK (Jun 2006) - GSK Biological's Vaccine Manufacturing Facility

If the pharma companies were not planning to benefit from Singapore's biomedical initiative, why would they spend good money to set up R&D departments here? I think that our current biomedical policy plays a crucial role in enhancing the pharma companies' confidence to invest in Singapore. This strengthens their belief that their investments will pay off in the future.

Thus, this data does not support Prof. Lee's second observation. I also think that it is too early to see the direct effect of our biomedical research, since foreign scientists have just arrived a few years ago, and even our fastest local Life Science student is not going to complete his or her postdoc until 2010.

Conclusion - Is the biomedical direction falling short of expectations?

Perhaps one of the underlying reasons behind this debate is that Mr. Yeo and Prof. Lee have different expectations of the biomedical policy.

A*Star's target for the biomedical sciences industry is to reach S$25 billion in manufacturing output and 15 000 jobs by 2015. Looking at the 2006 figures (S$23 billion and 10 571 jobs), the manufacturing aspect is doing well and right on schedule.

As for the research aspect, Mr. Yeo is not expecting any monetary payoffs yet. His successor Lt. Gen Lim Chuan Poh and IMCB director Prof. David Lane emphasized that the biomedical initiative is a long-haul effort that typically takes 10 to 15 years to blossom.

Thus, they are currently focusing on infrastructure building and personnel training. I am certain that all the leaders involved in the biomedical sciences want it to become successful and sustainable.

I believe that Prof. Lee also wants to get the best value out of this endeavour. She has highlighted potential pitfalls and challenges to the biomedical push, which demonstrates her passion about this area. However she has not explained why she feels pessimistic about the current strategy based on facts and figures.

As such I have no idea what her expectations are, and also cannot tell if whether her alternative recommendations will be better at meeting those expectations.

To sum up:

Fresh Brainz observed that there is room for improvement in the quality of research output, and that stellar performance in pharmaceutical manufacturing is not the direct result of research in Singapore.

The biomedical initiative is still in its foundation building stage and have not produced any spectacular results yet.

Based on publicly available data, Fresh Brainz cannot find any strong reason to consider the current research direction as a "mistake".

Why is Fresh Brainz interested in this debate?

On Monday 12th of February, Senior Minister Mr. Goh Chok Tong wrote to the Straits Times that:

"When you pour money into R&D, we all know this is for the long term. Are we moving in the right direction? Are we becoming too broad, or too narrow? These are issues that need to be discussed... But I personally welcome such a debate, provided it's conducted in a very objective and matured manner, without going into sensational name-calling."

It is in this spirit of intellectual debate that Fresh Brainz science blog strives to produce the most detailed and objective account of the discussion available on the blogosphere. I encourage everyone to support their opinions with as much relevant data as possible.

Would you like to know more?

Opinions of other bloggers

Aaron Ng (Hear ye! Hear ye!)
- The Intelligent Singaporean
- The Art of Dumbspeak
- Tan Kin Lian's Blog

Let This Mistake Continue? Part II

How to address the main question: Was it a mistake?

Fresh Brainz will use an analytical approach - which is to break this big question into several smaller questions and examine publicly available data to answer each of them.

1. Is the governmental effort spread too thin?

To find out if there are too many research areas or duplication of areas, I have consulted the research group descriptions of A*Star biomedical research institutes IMCB, GIS, and CMM.

The number of investigators in key research areas are summarized below. Please note that the figures are overestimates because some scientists are involved in more than one area.

Cancer Biology = 26
Regenerative Biology (eg. stem cell and developmental bio) = 21
Infectious Disease = 19
Technology Development = 16
Other basic biology areas (eg. structural bio) = 16

From this information you can see that the research strategy is centred on cancer, with regenerative biology, infectious diseases and technology development as other important areas.

Incidentally, hepatitis B is studied by researchers both in IMCB and GIS. The group in GIS is interested in hep B vaccine response whereas IMCB is more interested in hep B life cycle events.

There is no obvious duplication of research interests based on the research group descriptions. In addition there are unique areas in each institute. GIS has human genetics and system biology groups, IMCB has cell cycle control and translational research, CMM epithelial biology and genetic medicine.

In the newspapers, Prof. Lee wrote that she advocated "niche areas versus the shotgun approach we have adopted in Singapore."

Based on the distribution of researchers shown above, the current biomedical strategy does have a niche in cancer and regenerative research, though it is true that the research projects within each category is quite varied.

In addition, Prof. Lee observed that research is unpredictable, commenting that "even a combination of talented researchers, unlimited funding and cutting-edge equipment does not guarantee success."

As investors would know, when a situation is unpredictable, it is more prudent to diversify your portfolio rather than to put all your eggs into one basket.

So the recommendation should be exactly opposite - if the government has no confidence in the outcome of any one research area, they should have an even wider spread of research categories. To focus specifically on hep B and head injury as Prof. Lee suggests would mean high confidence that research in those areas will predictably pay dividends.

2. Are we identifying the correct niches?

Prof. Lee highlighted the importance of research in hep B, liver and stomach cancer, lupus, and head injuries. As I mentioned earlier, there are already A*Star groups working on hep B (plus at least two more researchers at NUS). There are also groups studying cancer and immunology.

As for head injuries, Prof. Lee is right to emphasize its impact to public health. It is the leading cause of death and disability for people under 40 in Singapore. This is a serious problem that should not be underestimated.

However, it is not a medical condition of the highest overall impact. This is a list of the top five killers of Singaporeans in 2005. (source: Ministry of Health website)

Total deaths = 16 217
Cancer = 26.4%
Ischaemic Heart Disease = 18.1%
Pneumonia = 14.9%
Cerebrovascular Disease = 9.9%
Accidents, Poisoning & Violence = 4.9%

Cancer and ischaemic heart disease are the top two, accounting for a whopping 44.5% of total deaths in Singapore. In contrast, acute head injury is only a subset of the 4.9% of people who die from accidents, poisoning or violence.

Based on this information, it is reasonable to have proportionally more research work done on cancer and heart disease. The current research focus on cancer and regenerative science does approximately reflect this.

In addition, there are already research groups in IMCB and CMM working on neural regeneration that is of direct relevance to brain injury. In fact one of the researchers at the CMM is a medical doctor interested in brain injury repair mechanisms.

Prof. Lee wrote that "At the National Neuroscience Institute, we have a good track record of head injury research and a comprehensive programme from molecular to bedside, from the acute stage to rehabilitation."

From the research group website at NNI, you can see that only one of the eight research labs focuses on acute brain injury. While the lab publication record in the past few years is good (including one paper to Neuroscience), it is hard to understand why this area should be chosen in preference to the other good labs working on Parkinson's and Alzheimer's Disease.

Although Prof. Lee said that head injury is "not a glamorous research topic", she also mentioned that ten major centres worldwide are doing serious research in it. This means that there are already many groups working on it.

There is no question that hep B and head injury are important research areas, and they are already part of the government's research portfolio. Perhaps Prof. Lee feels that there should be a few more research groups working in this area, which is fine.

However, based on publicly available information there is no strong reason to refocus the entire national effort into these two areas, unless Prof. Lee has privileged information that suggests otherwise.

3. Are foreign scientists sufficiently productive?

The performance of foreign talents is a sensitive topic which must be addressed.

Prof. Brenner (who is an honorary Singapore citizen) thinks that "as long as foreign talent leaves a legacy - which they now all do - this is the best way of spending our money. The worst way is what happened in the past when large numbers of foreigners came and worked here, obtained their training, and then departed, leaving nothing behind."

Prof Lee goes further: "We must get a fair deal out of them, and make sure that they are here to work for the good of Singapore and not just for science alone."

So, did we get a fair deal?

In this official report you can see that in 2006, BMRC research institutes published 335 papers in international scientific journals, twice as many compared to 2001. In addition, about 35% of these were in journals of impact factor greater than five. Since 2002, 15 patents have also been awarded in a number of areas such as virology and bioimaging.

This is a good result, but are we also producing higher quality scientific papers than before? One way to look at this is to examine the citations per paper of Singaporean articles and compare it to a city of comparable size, for example Hong Kong.

This is the result for the ten year period from 1994-2004:

Hong Kong
Total papers = 18 870
Citations = 163 337
Citations per paper = 8.66

Total = 36 506
Citations = 167 102
Citations per paper = 4.58

For a city state with only 65% of Hong Kong's population, we have nearly double their research output by volume, which is significant. However, the rate that our articles are cited is also significantly less.

Still, without yearly data specific to biomedical papers, and the latest figures for 2006, I cannot conclude if Singapore's biomedical investment is helping to enhance this area or not.

Dr. Lee asked "How many of the foreign stars have made any major discoveries after coming to Singapore?"

I think she brought up an excellent point. While a number of foreign scientists have produced excellent publications in the past few years (as high as Cell), producing major discoveries is entirely something else - that is very hard to do.

In addition to the scientist's productivity, in order to make a major discovery the creative millieu is also very important. I feel that Singapore is still lacking in this area.

Also it is difficult to assess the performance of foreign scientists in a vacuum since they often work together with local scientists. I am certain that the government must be using performance indicators to evaluate the performance of individual research groups, but this information is obviously not accessible to the public.

All I can say is that the figures suggest that combined efforts of scientists working in Singapore have produced steady results, but nothing spectacular has happened yet.

To be continued...

Monday, February 12, 2007

Let This Mistake Continue? Part I

In the past two weeks, a storm has been brewing in Singapore's biomedical scene.

A war of words has broken out between two powerful members of the elite: Mr. Philip Yeo, the chairman of A*Star, and Assoc. Prof Lee Wei Ling, the director of the National Neuroscience Institute.

Prof. Lee, who is the daughter of Minister Mentor Mr. Lee Kuan Yew (see my earlier article), was interviewed by Reuters when she expressed her concerns about the biomedical policy in Singapore.

She felt the current research efforts was not focused enough and should be concentrated on Asian diseases such as hepatitis B, autoimmune diseases as well as head injury.

She did not agree that Singapore should compete in the same areas as scientific powers in the West, and was skeptical of the strategy to employ prominent foreign researchers to spearhead the research effort here.

"How many of the foreign stars have made any major discoveries after coming to Singapore?"

She also said that the government may be having a rethink about its approach.

This prompted a quick response from the government stating that there was no change in the biomedical research strategy. A*Star also posted a report demonstrating that there was good growth in the biomedical industry. Government officials have unanimously expressed their support for the current biomedical direction.

Professor Sydney Brenner (see earlier article) noted that:

"Of course we are conscious that we need to focus because a small country cannot do everything. However the ills of Singapore, as we undergo economic development, are coming to be the same as other developed parts of the world - diabetes, cancer, heart disease, obesity and so on... My belief is that we should focus on the diseases that are rapidly increasing in incidence here, and those that have public health value."

During a media meeting, Mr. Philip Yeo said that Prof. Lee was a lone complainant, "one voice in the wilderness". He noted that Prof. Lee has not been to the Biopolis, which is the complex that housed key research institutes.

In the local newspapers, Prof. Lee countered "I would say that Mr. Philip Yeo, having never practised as a doctor, is strategising about biomedical research directions in an ivory tower. That is why he can dismiss hepatitis B and head injury as unimportant."

"This is not a matter of one-upmanship. We're talking about billions of dollars of tax-payers' money. I will not let this mistake continue."

She also revealed that she had received many email messages from local doctors and researchers who thanked her for speaking up.

The debate still rages on today. Many people in the local scientific community are talking about it. Ordinary citizens are taking sides on online forums regarding this issue.

As a Singaporean science blog, Fresh Brainz will examine the details carefully and concentrate on answering the main question.

Was it all a mistake?

To be continued...