Optimism for science in 2009 (and two budget-saving ideas)

As 2008 ends, I’m feeling very optimistic about the new year, principally because we here in the U.S. have elected Barack Obama, a new President who represents a dramatic change away from the policies of the past eight years. In the scientific arena, the Bush administration has been a disaster in more ways than I care to list. Not only have the Bushies politicized many, many areas of science, but their political views have almost always hindered or reversed progress in important scientific areas. But let’s look forward to the new year and to a new, re-invigorated U.S. science program.

Of course, the Bushies have also saddled us with an enormous debt burden, over $10 trillion dollars by one recent estimate (Harper’s magazine, December 2008). That number is so stunningly large that it might seem to leave no room for optimism – with such a gigantic debt, how can we hope for progress in anything, much less “discretionary” areas like scientific research?

Well, I’m still optimistic, but I know we’ll see little or no increase in the budgets of the U.S.’s top scientific agencies, including NIH, NSF, NASA, NOAA, and others. So here are two constructive suggestions for how to save significant funds at one agency, NIH, without adversely affecting scientific progress.

1. Get rid of the security fence and all the additional pointless security operations at NIH headquarters in Bethesda, Maryland. For those who haven’t visited NIH in the past few years, there is now a high metal fence (operational since 2005) surrounding the entire campus, and an elaborate security screening operation that every visitor must go through. Getting a car onto campus is now nearly impossible – every car has to be searched – and visitors have to plan for at least 20 minutes of extra time to get to their destination. This makes it much more difficult for NIH scientists to have visitors or to host conferences on the NIH campus – and it’s an utter waste of money.

Over at scienceblogs.com, there was an entertaining post on this topic last month by Mark Hoofnagle, who offered the opinion that “NIH security is run by paranoid idiots.” While I can’t say I agree with that sentiment, I share his feeling when he writes, “I hope in the next administration the first thing they do is tear down that stupid fence and treat the NIH like any other academic medical campus.” And if they get rid of all the accompanying security – which is really just “security theater”, as a writer in The Atlantic recently opined – they can save millions (probably tens of millions) of dollars per year.

2. Readers of my blog will probably guess my second cost-cutting suggestion for NIH: eliminate the National Center for Complementary and Alternative Medicine (NCCAM). This center was created at the behest of Iowa Senator Tom Harkin in 1992, not for any scientific reason, but because he personally believed in the efficacy of bee pollen as a medical treatment (see this NY Times article). There was never any need for this – any promising therapy can be studied in one of the existing Institutes, as has happened many times in the past. NCCAM has become a center for a raft of poorly-designed studies that would not pass review at the other institutes. Furthermore, in its 16 years of existence, NCCAM has failed to show that any “alternative” treatment works – the best that I can say about it is that some of its studies have showed that some pseudo-scientific treatments don’t work.

Like many government projects, though, part of NCCAM’s mission now is to perpetuate itself. So one of its major activities is to fund training centers that will educate health professionals in CAM treatments – even though its own studies have failed to show that those treatments work. This is how a government agency perpetuates itself. NCCAM is hopeless: its advisory council is required to include at least half its members from CAM disciplines such as “chiropractic, acupuncture and Oriental medicine. naturopathic medicine and massage therapy” – and when the board recently dropped below that percentage, CAM advocacy groups such as he Integrated Healthcare Policy Consortium and Academic Consortium for Complementary and Alternative Health Care wrote to NIH to complain. These groups are very active in promoting NCCAM, and they will continue to be as long as they make money by offering their various (and ineffective) alternative therapies.

Let’s get rid of NCCAM entirely before it’s too late. Former NIH Director Harold Varmus tried to put more scientific controls on the original CAM office, and Harkin responded with legislation that made NCCAM into a much-larger Center, with a budget that now exceeds $200 million. These funds could be put to far better use elsewhere in NIH. So without increasing the NIH budget, we could effectively increase the funds available for research by eliminating NCCAM.
(Note that others have suggested eliminating NCCAM too – see the excellent article by Wallace Sampson at Quackwatch).

I know that both these suggestions – modest as they are – are unlikely to be followed any time soon. But I will remain stubbornly optimistic that the Obama administration will choose a new NIH Director who has a strong, positive vision for the future of biomedical research, and who will be willing to take on anti-science interest groups – including Senators who want to promote pseudoscience – and start reversing the last eight years of policies. A few weeks ago the Obama administration announced that Varmus will be co-chair of its scientific advisory committee, and Varmus has shown in the past that he’s willing to take on NCCAM. Perhaps with stronger support from the President this time, he and others who agree with him will succeed.

Astonishingly stupid pseudoscience claim of the week

This week’s Parade magazine, distributed to millions of U.S. households in their Sunday newspaper, contains an article called “Alternative therapies that really work,” by Mark Liponis, an M.D. who’s promoting his books on how to live longer. I haven’t read his books, and based on this article, I certainly wouldn’t recommend them. He claims that he's found 3 alternative therapies that “have scientific backing and have passed the litmus test of rigorous medical inquiry” (Parade, Dec 14, 2008): acupuncture, meditation, and biofeedback. Let me just address the first one.

According to Dr. Liponis, “stimulating an acupuncture point in the toe may even help to correct the breech position of babies in the last trimester and allow more women to avoid C-sections, according to a study in the Journal of the American Medical Association.” This is so astonishingly stupid that I had to look it up. Is there really an article in JAMA that supports this?

Well, sort of. The study that Liponis refers to – I don’t know if he read it – is an old 1998 study by F. Cardini and H. Weixin (JAMA 1998;280:1580-1584). It’s a poorly done study, without placebo controls and without blinding (meaning the patients knew if they were in the “treatment” or “control” group), and it was done in a Chinese hospital.

What did they do? They burned the herb Artemisia vulgaris (mugwort) to stimulate acupuncture point BL 67, located beside the outer corner of the fifth toenail. Why? Because “traditional Chinese medicine” claims that this will encourage fetuses in breech presentation (feet down) to turn around so that they will be born normally; i.e., head first. Crazy, right?

Well, the 1998 study claimed that the treatment worked, although it was a small study and the authors admitted that there were methodological problems. To the lead author’s credit (but not to Dr. Liponis's), he conducted a follow-up study much more recently, this time in Italy, and reported on it in April 2005 in the British Journal of Obstetrics and Gynaecology (Cardini et al., BJOG 112(6): 743-747). This time none of the women were Chinese. And this time, there was no positive effect from this bizarre therapy. As the authors wrote, “The results of this study do not confirm those of the original study.”

So no, Dr. Liponis, stimulating an acupuncture point in the toe does not correct the breech position of babies in pregnant women. If you were even the slightest bit skeptical, you’d never have reported this in your article in Parade. It didn’t take me long at all to find the followup study. And the claim itself is so laughably stupid that it’s hard to see how an intelligent person could repeat it without embarrassment. But it’s clear from your article that you believe this nonsense.

I’ll bet that the Parade article – written by someone with the title “Dr.”, after all - convinces at least some pregnant women to seek acupuncture. Liponis should be embarrassed, but somehow I doubt that he is.

I'm thinking of making "astonishingly stupid quack claim of the week" into a recurring blog topic - the popular press seems to provide plenty of material for me.

Top 10 genome papers of all time

It’s December, and that means “top 10” lists are starting to appear for the year. I’ve put together a top 10 list, but it’s not just for the year 2008. The genome era is far enough along that we can now ask the question, “what are the top 10 genome papers to date?” The first complete genome of a free-living organism was published in 1995 (Haemophilus influenzae) and literally hundreds of genomes have appeared since then - thousands, if you count virus genomes.

How does one measure the importance of a genome to science? Of course I could give you my subjective list, but I was looking for an objective measurement, one that anyone would have to admit is reasonable. The one I chose – the obvious one, really – is the number of scientific citations that the original genome paper has collected. This measure has a bias towards older papers, because newer papers haven’t yet had time to accumulate as many citations, but all of the papers on the Top 10 Genomes list are at least 6 years old. I will revise this list in the future to accommodate updates in the citation counts.

The other question is how to count citations. After looking at several sources, I chose ISI’s Web of Science citation index. Google Scholar is another option, and I used it as well, but I found that Google is less accurate – it uses a heuristic method to collect citations, and it frequently double-counts references, especially for papers with large numbers of authors. I listed both counts in the Top 10 list, but the ranking follows ISI where there’s a disagreement.

So here they are! The Top 10 Genome Papers include 5 bacteria, 3 model organisms, and the two human genome papers right at the top. Not surprisingly, all 10 appear in Nature or Science (5 in each journal). All of the first authors are different, and three were authored by consortia without a traditional first author. And for those who want to argue about which of the two human papers deserves #1, ISI gives a clear edge to the publicly-funded effort, while Google Scholar, curiously, ranks the Celera Genomics effort (which I was part of) well ahead of the public project. My subjective list would have included the malaria genome paper (MJ Gardner et al, Nature 2002) – TB and malaria are the two greatest infectious disease killers of humans – but it came in at #12 using citation criteria. But it’s much newer than #9 and #10, so I'm betting it will move up in the future – stay tuned.

[Note that I’ve also created a separate web page for this list.]

Top 10 genome papers of all time

Criteria for inclusion: a paper must be the first description of the complete or near-complete genome of a species, and it must describe the DNA sequence as well as relevant sequencing methods and biological discoveries revealed by the initial sequencing of the genome. Rankings are based on citation counts, with the ISI Web of Science taking priority over Google Scholar, which is less accurate as it uses heuristic rules to gather citations. Counts from both databases are provided. Citation counts are current as of December 2008.

1. Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium
Nature 409:6822 (15 Feb 2001), 860-921.
Times Cited: 6,416
Google Scholar: 5,542

2. The sequence of the human genome
JC Venter, MD Adams, EW Myers, et al. (274 authors)
Science (16 Feb 2001), 1304-1351.
Times Cited: 4,588
Google Scholar: 6,502 [Note that Google places this paper at #1]

3. The Complete Genome Sequence of Escherichia coli K-12
FR Blattner, G Plunkett, CA Bloch, et al.
Science 277:5331 (5 Sept 1997), 1453-1462.
Times Cited: 3,327
Google Scholar: 3,625

4. Whole-genome random sequencing and assembly of Haemophilus influenzae RD
RD Fleischmann, MD Adams, O White, et al.
Science 269:5223 (28 July 1995), 496-512.
Times Cited: 3,075
Google Scholar: 2,651

5. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence
ST Cole, R Brosch, J Parkhill, et al.
Nature 393:6685 (11 June 1998), 537-544.
Times Cited: 2,858
Google Scholar: 3,163 [Note that Google places this paper at #4]

6. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana
The Arabidopsis Genome Initiative (143 authors)
Nature 408:6814 (14 Dec 2000), 796-815.
Times Cited: 2,689
Google Scholar: 1,728 (Google has real trouble tracking this "group author" name)

7. The genome sequence of Drosophila melanogaster
MD Adams, SE Celniker, RA Holt, et al.
Science 287:5461 (24 Mar 2000), 2185-2195.
Times Cited: 2,632
Google Scholar: 3,002

8. Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium
Nature 420:6915 (5 Dec 2002), 520-562.
Times Cited: 2,188
Google Scholar: 1,763

9. The complete genome sequence of the gastric pathogen Helicobacter pylori
JF Tomb, O White, AR Kerlavage, et al.
Nature 388:6642 (7 Aug 1997), 539-547.
Times Cited: 1,960
Google Scholar: 1,325

10. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii
CJ Bult, O White, GJ Olsen, et al.
Science 273:5278 (23 Aug 1996), 1058-1073.
Times Cited: 1,811
Google Scholar: 1,425 [Note that Google places this paper at #9]