Reactions

NIH on PubChem

C&EN recently received a letter by Jeremy M. Berg, director of the National Institutes of Health's National Institute of General Medical Sciences. Berg responds to an open letter by American Chemical Society President William F. Carroll posted on chemistry.org. Carroll's letter, published on Aug. 23, can be found at acswebcontent.acs.org/pdf/pubchem_open_letter2.pdf and is printed below in its entirety and without alteration. Berg's letter follows.

I want to update you on the status of our work toward a resolution of the NIH "PubChem" database issue, which was the subject of my June 20 letter to members (http://acswebcontent.acs.org/pdf/pubchem_open_letter.pdf).

According to NIH, PubChem has two purposes: to disseminate data from the molecular libraries screening center network and to create a comprehensive database of chemical structures with biological activities. While the first has drawn wide support, the second puts PubChem on course to fully duplicate a widely available database offered by ACS: the CAS Registry. ACS has invested heavily over decades to build and maintain the CAS Registry, which already includes the kind of data NIH is assembling in PubChem. We believe NIH should take advantage of and not replicate the CAS Registry to advance its molecular libraries initiative (http://nihroadmap.nih.gov).

ACS has been striving to work with NIH to arrive at a mutually beneficial solution. We have initiated more than a dozen good faith meetings, letters, e-mails, and phone calls with NIH, and I personally have had several face-to-face and telephone communications with NIH Director Elias Zerhouni. Despite assurances from NIH that PubChem will focus only on a limited set of "biomedically relevant" compounds, PubChem was recently expanded from 600,000 to more than 3 million compounds, most of which have no particular biomedical focus or affiliated data. We believe there is a better way to serve science, and we have proposed a truly collaborative approach to NIH.

ACS has offered to build, manage, and make available for free a database for NIH of data created both by its screening centers and all other compounds with associated bioassay data. ACS would contribute up to 15 staff and costs worth $10 million over 5 years. Because ACS already analyzes and manages data on virtually all compounds, this approach would save money and guarantee the high-quality data verification and standardization scientists expect. ACS and NIH would work together to disseminate any additional compound data in a way that utilizes, and avoids competition with, existing databases. Unfortunately, NIH has just rejected our offer, but we are studying their newly proposed alternative structure for resolving this issue.

In the end, by taking advantage of the CAS Registry, we believe NIH can:

• Avoid unnecessary duplication and gain cost savings that can be used for research grants.
• Satisfy federal policies that direct agencies to rely on substantially similar private services that can meet agency missions and avoid unfair government competition.
• Accelerate its molecular libraries initiative by utilizing a well-established, comprehensive, and high-quality tool for disseminating data on chemical compounds.

The issue is not whether to advance the NIH Molecular Libraries Initiative but how. Both the House and Senate appropriations committees have urged NIH to focus PubChem to avoid unnecessary duplication and competition with private sector databases. We are firmly committed to working toward a resolution that advances NIH's Roadmap, respects long-standing private efforts, and best serves science. I genuinely hope we can achieve this soon.

Sincerely,

William F. Carroll
President, American Chemical Society

I am writing in regard to the Aug. 23 open letter by American Chemical Society President William F. Carroll about discussions between ACS leadership and NIH staff regarding PubChem.

PubChem is intended to be "a new and comprehensive database of chemical structures and their biological activities ... that will house both compound information from the scientific literature as well as screening and probe data from the [NIH Roadmap for Medical Research's] Molecular Libraries Screening Center Network," according to NIH Roadmap documents. Each PubChem record includes only a chemical structure, available bioassay data, names provided by the depositor, properties such as molecular weight calculated from the structure, and links to the depositor and to other information within the suite of biomedical databases developed by the National Center for Biomedical Information (NCBI) at NIH. PubChem records do not systematically include experimentally derived properties, information about suppliers, information about synthesis and reactions, links to patents, or links to much of the chemical literature.

Both ACS leadership and NIH staff led by NIH Director Elias A. Zerhouni have worked hard to find ways to avoid unnecessary duplication between PubChem and private-sector databases such as those provided by Chemical Abstracts Service. As a chemist and the director of an institute that supports a large amount of chemical research, I have personally participated in essentially all of these meetings. Unfortunately, Carroll's letter misrepresents several important aspects of these discussions.

First, while PubChem is focused on biomedically relevant compounds, neither ACS nor NIH has been able to develop a suitable definition of biomedical relevance that would accurately guide what compounds should or should not be included in PubChem. And contrary to a statement in Carroll's letter, no assurances about the number of compounds to be housed in PubChem have been given.

Second, the expansion of PubChem from 600,000 compounds to more than 3 million compounds noted in the open letter is due largely to the inclusion of the ZINC database (C&EN, Feb. 14, page 8). This database was developed with support from a grant from NIH (R01GM071896) for the explicit purpose of making publicly available a large and diverse set of compounds for computational screening against biomedical targets. The NIH Roadmap Molecular Libraries Initiative explicitly includes support for developing and testing "new algorithms for computational chemistry and virtual screening." Thus, Carroll's statement that "most [of the newly posted compounds] have no particular biomedical focus" is inaccurate and misleading.

Third, while we appreciate the offer from ACS to build a PubChem-like database for free, the statement that this would result in significant cost savings to NIH is inaccurate. The great majority of the expense related to the development of PubChem involves the thorough integration of information regarding chemical entities with the biomedical literature in PubMed, protein structural information, biological activities, and other data housed at NCBI. This integration is where the great value of PubChem for biomedical research lies.

NIH continues to work with public-sector chemical information suppliers to advance the NIH Roadmap Molecular Libraries initiative and other research at the interface between chemistry and biomedical research. From our first discussions with ACS, NIH has offered to provide links from records in PubChem to records in CAS databases. This would allow researchers to navigate easily from the biomedically oriented information in PubChem to the extremely valuable chemically oriented data developed and maintained by CAS. Together, these and other databases will serve the research community as we apply chemical tools to understand biological systems and to improve human health.

Jeremy M. Berg
Director, National Institute of General Medical Sciences
National Institutes of Health
Bethesda, Md.

Chemical naming controversy

After carefully reading "Chemical 'Naming' Method Unveiled," I believe I must comment, because the article unnecessarily inflates a derivative work that is far from revolutionary in chemical structure description (C&EN, Aug. 22, page 39).

C&EN readers deserve to understand that International Chemical Identifiers (InChIs) are merely another chemical structure exchange format, just like SMILES (Simplified Molecular Input Line Entry Specification), Molfile, and the Chemical Abstracts Service Connection Table. It is not a naming method, and it is not a registry system that must identify both well-defined and ill-defined chemical structures and ensure that they are uniquely identified. InChI is simply a Molfile derivative work--it is a representation of and solely based on the MDL Molfile.

The term "dream team," which the article uses to refer to the InChI development team, would be more accurately applied to the scientists who perfected the connection table concept, which is at the heart of the CAS Registry System. For example, CAS's Harry Morgan, building on the efforts of Donald Gluck from DuPont, perfected an algorithm that converted a structure into a connection table, which became the basis for the CAS Registry System in 1965.

If this perspective had been given, the reader would have been able to easily see how InChI builds on the works of those named above and others. As the article says: "The string for naphthalene, for instance, is InChI=1/C10H8/c1-2-6-10-8-4-3-7-9(10)5-1/h1-8H. The first '1' refers to the version of the InChI software. The next segment of the string, C10H8, provides the molecular formula. The third segment is the connection table, which indicates how the atoms are connected." This so-called third segment, as I have already noted, is not in the least novel; it is a derivative of connection table work.

The comparison of CAS Registry Numbers and Beilstein Numbers to InChIs reflects a lack of understanding regarding what lies behind these numbers. The CAS Registry Number is a concise identifier and provides the link between chemical nomenclature, the CAS Connection Table that describes the atom bond linkages of a chemical structure, and the molecular formula. It was never intended to be a structure exchange format that could be "decoded" to understand the chemical structure.

It is true that InChI is an open format, while the CAS Connection Table is a proprietary format. However, the CAS Connection Table must describe all types of chemical substances, because it is at the heart of the CAS Registry System, which encounters all possible substances described by scientists (or chemists, biochemists, molecular biologists, and so on); it is a unique identification of chemical substances. The developers of InChI acknowledge that InChI is just a way for computers to exchange information about chemical structures.

Eileen Shanbrom
Manager, Online Services, SciFinder and Web
Chemical Abstracts Service Columbus, Ohio

Confusing caption

The photo caption in the story "Arsenic in Rice" that reads "HIDDEN TOXIN Rice grown in the U.S. contains arsenic" is very misleading (C&EN, Aug. 8, page 17).

There is nothing extraordinary about the fact that arsenic is in rice. Arsenic is in every grain on the planet--regardless of national origin. It is a naturally occurring element found in nearly all soils.

Keep in mind that approximately 15 to 25 µg of arsenic appears to be a requirement in human nutrition, according to many chemistry textbooks and scientific papers. This should dispel the alarmist notion carried recently in mass media stories that the mere presence of arsenic in rice or any food is a cause for alarm, as was implied in the photo caption.

David Coia
Arlington, Va.

Redefining 'ACS'

The American Physical Society has voted overwhelmingly (76% in favor) to change its name to the American Physics Society. Now it is time for ACS to get on board. Either "American Chemist Society" or "American Chemistry Society" would be acceptable. Let the American chemicals get their own society.

Dana D. Dlott
Urbana, Ill.

Technicians and training

Ernest Lee Rector III is to be commended for his education and experience in the field of chemistry (C&EN, Aug. 8, page 11). It is true that many of us with Ph.D.s or B.S. degrees in chemistry rely on chemical technicians to get the job done, and in my experience, chemical technicians are appreciated for their contributions throughout the industry. And I agree that including associate's degrees as a category in ACS publications is reasonable.

I take issue, however, with Rector's implied suggestion that the difference between his associate's degree and a B.S. degree boils down to "art appreciation" courses and that his education provided "as much, and in some cases more" chemistry-related education as for those with B.S. degrees.

That's hogwash. Anyone with a B.S. in chemistry has at least two years of 300- and 400-level courses beyond what a two-year associate's holder gets, including a year of physical chemistry, inorganic chemistry, and other advanced courses with laboratories.

B.S.-degree holders have also taken at least a year of calculus and calculus-based physics. In fact, many B.S.-degree holders finish the "breadth courses" in their second year, even while taking all the chemistry courses an associate takes; they then spend their final two years taking only chemistry and other science courses. Add another two years for a master's degree or at least four for a Ph.D. While the associate's degree in chemical technology provides a student with sufficient background to assist in the laboratory, there is simply no way the education compares to that of a B.S. or advanced degree in chemistry.

Is this grounds for snobbery on the part of B.S. or advanced-degree holders? No. But if Rector ever wants others to think that his chemical education is as complete as it is for a B.S. degree, all he has to do is enroll for a couple more years of school, study hard, and get his own B.S. degree in hand.

Scott A. Heidecke
Eugene, Ore.

Rector's letter was about "articles and polls dealing with levels of education." He says his degree level is omitted or relegated to "undergraduate student" or "less than bachelor's degree." He says he has a difficult time participating in these polls; yet he is a member of ACS and has an A.A.S. (associate in applied science) degree.

I am glad Rector is a member of ACS and has the desired A.A.S. degree; congratulations that he became a technician by design, not by default. But he did not say whether he is a member of ACS's Committee on Technician Activities (CTA). Practicing chemical technicians should not only be members of ACS, but also members of CTA. I hope that I will see Rector's name among new members of our division in the next issue of CTA's quarterly publication.

Who am I to talk? In 1957, I was hired to lead an A.A.S. program at Ferris State College, a program that trains chemical technicians academically. At that time, there was no place in ACS for those who graduated from my program. Today, graduates of the program, which I led for 30 years, are welcome to join ACS. During my first year of teaching, one large Michigan-based company said that they had never hired a chemical technician and could see no reason why that practice would not continue. A few years later, they hired three-quarters of my class, and the next year they hired 100% of my A.A.S. graduates. The A.A.S. chemical technician has come a long way, because they are needed by the chemical industry. Look at John Engelman, chair of CTA; he holds an A.A.S. degree.

There are many places for the A.A.S. chemical technician in ACS, and those opportunities continue to expand. I, too, hope that starting salaries of the A.A.S. chemical technician will soon be published in the pages of C&EN.

Norman G. Peterson
Big Rapids, Mich.

Where are the jobs?

I just received the issue containing the annual salary and employment survey (C&EN, Aug. 1, page 41). The question in my mind is, where are the jobs? There are a plethora of articles detailing how we do not graduate enough scientists, how other countries are turning out more doctorates than the U.S., and how we need to relax immigration laws to allow more foreign-born scientists into the U.S.

It has been two years since I graduated with my doctorate in chemistry. In those two years, I have sent out thousands of résumés and made countless phone calls, and yet I am still waiting for my first employment as a chemist at the doctoral level. The closest employment that I have had using my skills was teaching one semester of freshman chemistry at a local community college. However, this was only a part-time job.

I went deeply into debt to obtain my doctorate, but in the two years since graduation, I have been working in call centers as a customer service representative. My salary has ranged from $5.00 to $11.50 per hour. If I had not had the help of my wife's salary as a nurse and the help of relatives, I would be bankrupt. As it is, I have used all of my retirement funds to help pay back school debts. I do not have the resources to travel to exotic cities and stay in expensive hotels to attend ACS meetings to hand out résumés. I have to be content with using either the mail or the Internet.

I noticed that the median salary for a doctorate in my region is $90,000 per year, I would be willing to work at one-third of that just to get back into the laboratory. Again I ask, where are the jobs?

F. William Weaver
Tempe, Ariz.