Critiques of Arsenic-DNA paper published in Science

Almost 6 months later from the publication of the original paper.

Eight critiques!

Another case of peer review out in the open.

Arsenic-based life forms: Fact or fiction?

The biggest science news of the past week probably has to be NASA's press release claiming to have isolated a bacterium that substitutes arsenic for phosphorus on its macromolecules and metabolites. (Wolfe-Simon et al. 2010, A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus.)

As things stand, many scientists are openly skeptical of the claims made in the paper.

That is understandable, given the potential impact on biology. If the results are shown to be right, this might open a whole new field of research on arsenic-based life forms (and possibly the Nobel Prize in the near future). E.g. The discoverers of graphene were awarded the 2010 Physics Nobel a mere six years after their publication in Science.

And the authors' response to the online critics?

"If we are wrong, then other scientists should be motivated to reproduce our findings. If we are right (and I am strongly convinced that we are) our competitors will agree and help to advance our understanding of this phenomenon. I am eager for them to do so." - Ronald Oremland, US Geological Survey.

Heh, the scientific method is at work here.

This whole episode reminded me of a question back in the days of my JC S-paper chemistry class where we were asked to suggest alternative elements that could potentially replace those currently in use by nature. Can we substitute carbon with silicon? Phosphorous with arsenic? Would there be any problems with these changes under earth's atmosphere and conditions?

Maybe I should revisit my old A level notes (if I still have them somewhere) to look for old theories to test. Maybe I can get something useful (like a Science publication) out of them. Like the SN2 reaction mechanism. Who could have thought there would be an unexpected 'roundabout' mechanism in addition to the traditional 'inverted umbrella' pathway?

The video that all prospective PhDs should watch

Self-explanatory.

Mixing humor and heartbreak, Naturally Obsessed: The Making of a Scientist delves into the lab of charismatic professor Dr. Lawrence Shapiro, and follows three irrepressible graduate students on their determined pursuit of a PhD and scientific success. As if the pressure of scientific discovery isn’t enough, the students are also competing in a worldwide race to be the first to publish their findings. Their challenge: to decipher the structure and mechanism of AMPK, a tiny protein that controls the burning and storage of fat. Their road to success: years of trial and error, unflinching dedication, rock-climbing, rumors of pickle juice, and the music of The Flaming Lips.

Whistleblowers suffer from collateral damage too

Science reported the case of Elizabeth Goodwin, a former UW-Madison associate professor of genetics who pleaded guilty to a charge of scientific misconduct for falsifying data in a grant application to the NIH.

What is interesting (and sad!) though is not so much about sentence meted out to Goodwin (most likely just a fine and a ban from receipt of federal grants for 3 years), but the fate of her ex-students (ie. the whistle blowers):

The university praised the students for having done the right thing. A university investigation subsequently concluded that Goodwin had falsified data on grant applications and cast doubt on three papers, all of which were later cleared of any problems. Goodwin resigned. But the outcome for several students, who were told they had to essentially start over, was unenviable. One, Chantal Ly, had gone through 7 years of graduate school and was told that much of her work was not useable and that she had to start a new project for her Ph.D. (The reason wasn't necessarily because of falsified data but rather, Ly and the others thought, because Goodwin stuck by results that were questionable.) Along with two of the others, she quit graduate school. Allen moved to a school in Colorado. Just two students chose to stay at UW.

One of those who left reflected about the case in the Science story published in 2006. "Are we just stupid [to turn Goodwin in]?'" Sarah LaMartina said. "Sure, it's the right thing to do, but right for who? ... Who is going to benefit from this? Nobody."

The system as is right now is heavily tilted to the PI's favor. Principal investigators have too much power over the fate of their graduate students' and postdocs' scientific careers.

The PI has the power to direct the efforts of his/her students and postdocs, choose their projects, set their hours, tell them who to work with, decide whether their data is worth keeping or suitably labeled as junk, decide whether, when, and by whom their results are presented, and so forth. The PI controls all the resources the graduate students need -- funding, training, even access to other faculty in the department.

Even if he/she is to fall in disgrace, the students and postdocs won't be able to get away unscathed, as this episode demonstrates. A professor in my PhD institution once gave us (then 1st year grad students fresh out of college) this piece of advice:

"Your relationship with your PhD and postdoc advisor is most important, even more so than your spouse, especially if you stay within the scientific community. You can divorce the latter, but your link to your advisor(s) is permanent. So make sure you choose the right one."

Academia (Tenure) as a Profzi Scheme

The headline hogging news to affect academia (at least in the US) this past weekend is the Amy Bishop Anderson tenure-denial mass murder case. Much had been discussed about about her sanity and intentions, and I won't dwell into them.

But it has brought to the forefront the issue of tenure for professors (the ultimate prize for all academia-focused postdocs and grad students). Even getting a tenure-track assistant professor position these days is highly competitive. Anecdotal stories by faculty search committees across a wide spectrum of disciplines tell of 500 - 700+ applicants per advertised vacancy.

A friend of mine, in his 4th or 5th year as a postdoc, was recently told that there is nothing else that he can do to improve his chances for a faculty job but to publish in Science or Nature. This was not for a job at Harvard or Standford[sic] or anywhere close. It came from people well towards the end of their career, who are sitting on the hiring committees and who have never ever published in Science or Nature.

Unrealistic expectations and pressure...

- Foreign and Female in Science

I chanced upon the webpage of someone who turned down a Singapore NRF to be an assistant professor in South Carolina (as of Feb 2010). He had a Science paper as a 1st author coming out of his postdoc in a respected lab and many others in well regarded high impact journals. Yet for all his efforts he only accepted a position at the University of South Carolina. No offense to South Carolina, but if someone who is highly productive with a Science paper can only get an offer from South Carolina then what about the rest of us with no Science or Nature publications?



On a side note, it is telling that Singapore's supposedly 'prestigious' research fellowship ranks below that of a tenure track assistant professorship at a second-tier American university. Why else would he choose not go to Singapore with a guaranteed seed funding of up to US$1.5 million in the first three years? I certainly do not think SC would be able to match Singapore's cash offer. Most US research faculty start-up packages in the sciences/engineering are usually in the region of about US$300K - 600K for up to five years.

*

Edit (24 Feb): Scientific American published a highly critical assessment of the state of the US academic job market.

Many Applicants, Few Academic Posts

The competition for science faculty jobs is so intense that every advertised opening routinely attracts hundreds of qualified applicants. Most PhDs hired into faculty-level jobs get so-called “soft-money” posts, dependent on the renewal of year-to-year funding rather than the traditional tenure-track positions that offer long-term security.

...But scientists are not generally recruited from the average students, Salzman notes, but from those with the top scores, of whom America has large numbers. Compared with the products of Asian secondary schools, American students “are free thinkers,” says Vivek Wadhwa of Duke and Harvard Universities. “They didn’t spend the last 12 years of their lives memorizing books…. They’ve spent the last 12 years dealing with real problems and solving them. [In America], you can walk up to your teacher and tell her that she’s wrong or he’s wrong.” In Asia, he continues, “you wouldn’t dare do that.”

...The American approach of temporarily funded labs staffed largely with student and postdoc labor offers several important advantages. It enlists the finest talent at the nation’s great universities in projects that meet national priorities set by the funding agencies or by Congress. It permits flexibility in selecting studies and researchers and the opportunity for rapid changes in direction because the grants are for specific purposes and last only a limited number of years. It elicits the best ideas and best work from highly motivated scientists because it chooses the grantees through a competitive system of merit rankings done by peer committees composed of academic experts in each field who serve as part-time judges. It frees the government from owning the labs and managing their staffs. And it allows federal dollars to do double duty—produce research results and provide education and support for the graduate students and postdoctoral associates who work on the projects in labs run by professors who pay them out of the grants.

This system produces superb science, but it has several serious drawbacks from the standpoint of recruiting and retaining scientists. First, it makes the funding of any particular lab inherently unstable and dependent on winning repeated grants and renewals, which places individual careers at the mercy of annual competitions. In times of very tight federal budgets, such as the present, this means that many labs, and even many well-established scientific careers, do not survive. Second, it produces not only educational opportunities and research results, but also a constant stream of newly fledged young researchers who need opportunities to start their own careers. “The way that U.S. staffs its labs puts so much pressure on the system to absorb the continual new cohort. And we haven’t had much luck in absorbing it,” says Georgia State’s Stephan.

Modern Science is One Big Pig Trough

And not just academia (administrators, faculty, postdocs/grad students) is beholden to it. There is also a huge related industry (annual sales in the billions of dollars) led by the lab equipment suppliers. So if you are one such company, how do you go about getting some of that stimulus money?

You trawl the top-ranked academic journals and send out unsolicited advertising emails to the authors of recent publications.

Dear Dr. takchek,

I read your paper in (kick-ass high impact factor in its subfield journal), and I wanted to send you a short note on recent technology that may be of interest.

We have been working with a number of research leaders in Nanomedicine and nano-drug delivery research looking to quantify nanoparticles in live cells. This effort led to the development of a novel system called "complicated-sounding name that only specialists in the sub-field understand (with acronym)"...Insert the advantages and coolness of this new technology...and must end with your targeted audience in mind...This technology has been specifically designed for use in nanomedicine, nanotox and related nanoscale investigations.

We are actively involved in supporting funding and grant submittals for the NEW (April 2009) Obama funding at NIH and NSF. If you are considering applying for some of the NEW $8.2 billion of grants for equipment PLEASE let us know. We can help!

Best regards,

On the other hand:

NIH received ~21,000 applications for the stimulus funds. They expected 1,500 and predicted 200 Challenge Awards will be offered. So the rejection rate could reach 99%. (Science, 2009, 324, 5925, pp. 318 - 319)

Amazing Depressing eh? I think it is easier to get into Harvard college than to win one of these NIH Challenge Grants.

Obama's New Deal for Academia

I will be honest upfront - things were really looking bad for us folks in academia (and pretty much everyone else too) in last few months. Well, they still are, but things are looking up with the passage of the American Recovery and Reinvestment Act (the economic stimulus package) signed by President Obama on Feb 17.

In an email last semester, my PhD advisor actually had to send out a letter to the group (in addition to a pep talk during the regular group meetings) with encouraging words:

Dear group,

This (financial crisis) is a good opportunity to clarify and reinforce the positive things about our group. First of all, my primary concern is, and will continue to be, the welfare of my students. I will do anything (legally of course) and everything to keep your work going and with the best resources possible, and to help you make the most of your time here.

I know that situations like this can cause stress to rise and may lead to uncertainty among the group. First, I want to assure you that this will not fundamentally alter our ongoing research plans.

Secondly, it is obvious that the composition of our group is changing rapidly…mainly because of graduations. This is a good thing and it is normal. People are supposed to graduate and leave. So, there will be turnover in any organization. I wish that the group number were not fluctuating so largely, but that is only partially within my control. Grants get funded at unpredictable times, and about 5 years ago I had a lot of grants get funded all at once. I had a bunch of students join the group. Now those students (you know who you are) have finished or close to finishing.

The group size is small right now, and it’s going to get smaller temporarily, and this is intentional.

Let me explain:

In order to avoid this type of fluctuation in the future I have been attempting to take on only 1 student a year for the past two years. I have been writing only enough proposals to support this rate of growth (so I don’t have to take 3-4 people at once). So, this is part of a greater plan to provide more stability in the future.

Thirdly, about funding: Professors who have been in this business for 40 years (like the department chair) will tell you that they have never seen funding as tight as it is right now. So, writing only a few new proposals to grow the group 1 student per year is risky, which is why I was not planning originally to take on 2 this year. Another issue is that my current projects are non-overlapping –purely by chance – the main projects get renewed at the same time (January) each year. This means that at the end of the year I have to be careful – just like you do at the end of each month. So, if I look over your orders more carefully it is simply for this reason. It doesn’t mean that support for your project is going away and should not be a cause for your concern. I’ll take care of, and worry about, the funding. You guys (and gals) can worry about the research.

The quantity and quality of research output, and the type of job you get, and how long it takes you to graduate is rarely a direct function of the quantity or type of funding anyway. It is true! Some of the most highly-cited papers have come from poorly-funded research, not only in my group but in general throughout science. And some of the most well-funded work has produced few papers. I have other sources of funding to keep ideas afloat between big grants. It is not an impediment and I have always gotten the funding I sought.

When you go on a job interview, no one will ask how much funding your advisor had! What is important are the indicators of the quality and quantity of your work: how many papers, presentations and in what journals / conferences.

I am confident that our research is on the cutting edge and that each of your projects is going to lead you to an exciting career. For example, the number of citations of previous students’ work from my group is at an all-time high. It is among the highest of any associate professor at this university. My h-index is 20.

I will talk more about these things at our next group meeting, and until then my door is of course open to speak about this.

Regards,

Prof X

Yesterday my postdoc advisor had the whole group summoned:

Congress had given federal granting agencies (NSF, NIH, DOE) stimulus money for colleges to spend. There are opportunities for us in getting some of that package money. I want to help Congress spend those money and I want each and everyone of you to come up with ideas by Friday on how to tack on our existing NSF, NIH and DOE grants with more funding.

Focus on the "near-term" and ready to start projects, as these are especially advantaged in this environment.

Government-Wide Timeline

All agencies are under significant pressure to begin distributing the funding in the stimulus bill to States, organizations, and individuals as quickly as possible. The overall timeline announced by the Administration for the next few months is:
• February 19, 2009: Federal Agencies to begin reporting their formula block grant awards.
• March 3, 2009: Federal Agencies to begin reporting uses of funds.
• May 3, 2009: Federal agencies to make performance plans publically available; to begin reporting on their allocations for entitlement programs.
• May 15, 2009: Detailed agency financial reports to become available.
• May 20, 2009: Federal agencies to begin reporting their competitive grants and contracts.
• July 15, 2009: Recipients of Federal funding to begin reporting on their use of funds.

In addition, the Office of Management and Budget has set targets for implementation of programs by the agencies. Individual agencies have additional deadlines; for example, NSF, NIST, and NASA have been directed to deliver a spending plan to Congress by April 18, 2009.

I live in exciting times...plus it helps that I am in involved in the development of new, clean, renewable energy sources, one of the hottest areas (pun unintended) of research right now.

Innovation Video Contest - via Youtube

Got this in my mailbox:

The Task Force on the Future of American Innovation is sponsoring a "You Tube" video contest to highlight scientific innovation in America. Interested individuals are encouraged to create a three-minute video that demonstrates how scientific discoveries resulting from federally funded research in the physical sciences have changed our lives. Students are especially encouraged to use their creative skills and participate in the contest. The deadline to enter is the 10th of September.

The top five videos will be viewed in the U.S. Capitol on October 4, 2007 during the 50th anniversary commemoration of the launching of Sputnik. The grand prize winner will receive $1000 and an all-expenses paid trip to Washington for the October 4th activities.

The Task Force on the Future of American Innovation is a coalition of organizations from industry and academia which promotes increased federal support for basic research in the physical sciences and engineering. For more information about the Task Force and for complete contest rules, visit: http://www.futureofinnovation.org/

For a video presentation on the competition, visit: http://www.youtube.com/watch?v=tuGBNNCwkfs

As a tip to my readers who are interested in participating, I recommend this site as an initial reference.

Life Sciences Hub, or Hype?

This has finally made it to the papers. On Today, 9 Oct 2006:

The Life Science Conundrum

After the hype, grads now realise that there’s no place for them in the
industry

Loh Chee Kong
cheekong@mediacorp.com.sg

IN 2002, when Singapore universities had barely begun producing their own life sciences graduates, Mr Philip Yeo, chairman of the Agency for Science, Technology and Research (A*Star), famously rattled those unndergraduates when he said that they would only be qualified to wash test tubes.

But four years on, armed with their Bachelor’s degree, some of these graduates are learning the truth of his words the hard way. Many from the first cohort have ended up in junior research positions or manufacturing
and sales jobs in the industry - positions that do not require a life sciences degree. Others find themselves completely out of the field.

Said Edmund Lim, 27, who graduated two years ago, and now works as a property agent: “One of my classmates is working illegally in Australia, peddling psychotropic drugs to clubbers. Many of my classmates have gone into teaching. Others are in pharmaceutical or equipment sales.”

Another life sciences graduate, who declined to be named, found a job recently at a tuition centre, after failing to land research-related positions for over a year despite numerous job applications.

Already an established base for pharmaceutical manufacturing, Singapore has been trying, in the past five ears, to move beyond manufacturing to more high-end research that is “value-added”.

According to the industry’s annual reviews compiled by A*Star and the Economic Development Board’s Biomedical Sciences Group (EDB BMSG), an average of a thousand new jobs were created annually for the past five years. Last year, there were 10,200 manufacturing jobs in the industry, almost doubling the 5,700 jobs created in the then-fledgling sector in 2001. By 2015, EDB targets the number of such jobs to hit 15,000.

But the booming figures mask a Catch-22 situation: The current shortage of PhD holders in the biomedical sciences cluster is hampering Singapore’s bid to attract multinational companies to move their high-end research projects here. Without a PhD, most of Singapore’s life sciences graduates are only qualified to work as research assistants.

And both graduates and diploma holders vie for these positions that could pay less than $2,000 a month. In the industry’s manufacturing sector, life sciences graduates compete against their peers from other general sciences and engineering disciplines. They face even stiffer competition in the sales sector, where paper qualifications take on less significance.

A*Star’s Biomedical Research Council oversees and coordinates public sector biomedical research and development activities. On the surplus of life sciences graduates, its executive director Dr Beh Swan Gin told Today: “It is not a situation that can be easily communicated, as there are many factors involved. Simply put, a PhD is essential for progress as a researcher. And there are still not enough Singaporeans pursuing PhD studies.”

Adding that the local universities should not pander to the students’ demand for the subject, Dr Beh said: “The job market of today and tomorrow, is the market the universities should focus on. The manufacturing and commercial jobs have always been there, albeit there are more of these now. NUS (National University of Singapore) and NTU (Nanyang Technological University) should get better data on the demand for life science graduates at the Bachelor’s degree level.”

In 2001, NUS’ Science Faculty rolled out an integrated life sciences curriculum and NTU started its School of Biological Sciences (SBS) a year later. Meanwhile, the polytechnics also introduced more life sciences courses. Thousands of students jumped on the bandwagon, with demand outstripping the supply of places in these courses.

Professor Tan Eng Chye, NUS’ Dean of Science - who believes that it could take another five years for the industry to establish itself - acknowledged that his school’s intake of life sciences undergraduates was “a bit too high”.

“When we started offering a major in life sciences in 2001, 550 students took up the programme. For the subsequent intakes, the number stabilised at about 450. But we would be more comfortable with about a hundred less,” said Prof Tan, who added that many students were “unrealistic” about their job prospects.

Said Prof Tan: “A lot of students were probably all hyped up to look for R&D jobs. And when they can’t get such jobs, they could be disappointed. If they want to do research, they should further their studies.”

Nonetheless, some headhunters, like Kelly Services’ Lita Nithiyanandan, predict that it is “only a matter of time” before these “highly valued” graduates find willing employers. Said Ms Nithiyanandan: “As most of these multinational life sciences companies have recently set up or moved their R&D centres to Singapore, they require senior and experienced research professionals at this stage to streamline operations and get compounds approved fast for clinical trials. Once these centres are more established they will definitely need fresh graduates for researching new compounds.”

She added: “Overall, Singapore’s biomedical scene is evolving as a mature hub for Asia Pacific. This would create opportunities across the board for skill sets through the value chain from fresh graduates to mid-level research and analysts to high-end PhD professionals.”

There aren't that many (industry) jobs at the PhD level in the bio sector too. The research's hot, and many (US) professors can get the funding they need. But that doesn't translate into jobs for the doctoral graduates in the US. Many will end up doing post-docs for many years.

I should know - looking at my PhD friends in the (pure) life science majors. The ones having the best and most offers are the Mechanical, Chemical and Electrical engineers.

(Exclude mgt consulting and i-banking.)

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