MAIL

G-CSF and leukemia

In "A waiting trial," ¹ which explores whether Doug Berman's participation in a clinical trial of cardiac stem cells triggered his diagnosis of acute myelogenous leukemia (AML), there is certainly at least some biological plausibility that G-CSF might have played some role in the development of AML in this patient. G-CSF and other growth factors have been demonstrated to stimulate leukemia cells as well as normal granulocyte precursors in vitro. However, the short latency (13 months) argues against a connection, as do the several controlled studies demonstrating no shortening of remission in AML patients treated with G-CSF versus those not treated with G-CSF.

As Mr. Bergman was an auto mechanic for 35 years, I would wonder at his use of benzene and/or other organic solvents as degreasing agents (which auto mechanics commonly use), as chronic exposure to benzene and other organic solvents are known risk factors for AML.

David B. Karpf
Stanford University Hospital
Stanford, CA
dkarpf@metabolex.com

I found the reporting in this article to be very even and thoughtful with one exception. I found the following statement inappropriate: "The next day, doctors jabbed a needle filled with either saline or Bergman's own CD34+ cells – the trial is placebo-controlled and double-blinded, so he doesn't know which – into his heart 10 times to deliver the cells."

"... jabbed a needle" does not raise the level of the scientific discourse and seems inflammatory to me.

As a physician-scientist who thinks every day about how to inform volunteers of risks in clinical trials, I can guarantee you that this kind of language could close the minds of most level-headed people. It also reverts us back to the concept of volunteers as "subjects" and "guinea pigs," rather than the informed participants who are required to advance medical science for the public good.

Steven Smith
Pennington Biomedical Research Center, Louisiana State University
Baton Rouge, LA
smithsr@pbrc.edu

References

Fixing the female job pipeline

Re: "Am I sexist?" ¹ It was encouraging to see someone recognize and take steps to deal with gender bias in the sciences. At the University of Texas at Austin, the percentage of tenured women in the natural sciences is 10%, essentially unchanged over the last 12 years. This statistic is not a pipeline problem, since women have received 30% to 40% of the PhD degrees in science in the United States for the past 14 years, a period of time sufficient to allow women to move into tenured positions. The paucity of senior women even extends into the School of Biological Sciences at the University of Texas, where women represent less than 20% of the tenured faculty, despite hiring from a pool in which women comprise more than 40% of those holding PhD degrees. Our data support the findings of the National Academies that cultural bias is a basis for gender inequities in the sciences and engineering.

Furthermore, senior faculty women face a dramatic concrete ceiling with regard to salaries. When merit raises in our department were distributed without defined criteria for performance or evaluation, more than $60,000 was distributed to male full professors, while the females received only $750. Our efforts to highlight the blatant nature of the salary discrepancies led to a gender-blind analysis by a committee of faculty from outside the department. The results showed a striking lack of correlation between women's salaries and their accomplishments, clearly demonstrating the ceiling effect for the salaries of female professors.

We suggest that gender inequities in the salary arena would be eliminated if the same objective and quantitative approaches as those applied to other scientific data were used for the determination of salaries and distribution of other faculty resources, irrespective of gender. Faculty must insist on the use of objective criteria for merit reviews and on the use of outside committees to monitor and evaluate the data, as we have begun to do at our institution. Following review, a female assistant professor's salary was adjusted to the same level as a male's, and the salaries of the female full professors were partially corrected.

However, such periodic catch-ups leave females lagging far behind in total compensation and place an additional burden on women faculty to draw attention to the inequities. Only when bias is eliminated from the system for salary and resource allocation will the morale for female faculty improve, encouraging other women to enter and thrive in the sciences.

Shelley M. Payne
Jaquelin P. Dudley
Rasika Harshey
Karen Artzt
Institute for Cellular and Molecular Biology
University of Texas at Austin
payne@mail.utexas.edu

I am one of the full-time working mothers that you speak about. I was hired 10 years ago into a biology department, and I was the last woman hired even though we have made roughly 9 appointments (at or above Lecturer) since. We have 27 academics (Lecturer to Professor) in our department, four of which are women (ca. 15%). Only one woman is at the level of Professor (hired in at that level), the rest of us are Senior Lecturers. I do much to help "mentor-up" the next generation, but I don't see a clear and promising path for myself. If I put less time into my teaching to help my students (i.e., the feel-good things that we don't really get much credit for at promotions rounds), I could publish more surely.

So what to do? I am between the proverbial rock and hard place: the commitment to students and quality teaching versus being more selfish. One way would be to recognize contributions to the university as well as publications – those committees, services, and initiatives that fall to us to do because no one else will do them. Or, perhaps we need to learn to "just say no" as so many of our colleagues do.

Chrissen Gemmill
University of Waikato
Hamilton, New Zealand
gemmill@waikato.ac.nz

I've heard women at research institutions complain that while their institution may have family leave policies, their grants do not: No extra time or funds are provided to keep a lab going while a female PI cares for a new child or infant. Let's also remember that women are disproportionately the caregivers for elderly parents or disabled siblings, so family leave should be flexible. NIH and NSF should see what they could do to make their funding mechanisms more family-friendly.

Elizabeth De Stasio
Lawrence University
Appleton, WI
destasie@lawrence.edu

Peer review and oral tradition

In his column "Telling science's stories," ¹ Steven Wiley makes excellent points regarding the reasons behind the missing information in the literature that is passed on only by verbal communication.

The current functioning of the peer-review system might create an additional major reason for the absence of certain information from the literature. Peer review forces researchers to tell a simplified story. As much as we favor parsimonious explanations, complexity can often be the reality in biology. But the complexity needs to be weeded out if the work is to be understood by reviewers in a short enough time for them to give a stamp of approval. Peer review leads to partial truths in the literature, with much of the reality left in the researcher's notebook to be passed on only via the oral tradition.

If peer review could move beyond recognition of sound bites and oversimplified stories, the reality of biology would be much more readily available in the literature. Perhaps switching to a nonanonymous peer-review system would go a long way to reducing the need for the oral tradition.

Colin Anderson
University of Alberta
Alberta, Canada
colinand@ualberta.ca

Shouldn't the public care?

Re: "Is the US party over?" ¹ I do believe that international competition in science and technology is good, but I am surprised that it has not served to spur this country into playing the game more rigorously.

We hear repeatedly the cry for improved education in science and math. This is, in part, due to the need to continue developing players for the worldwide competition in science and technology. Participating in research (whether undergraduates, graduate students, faculty, or citizen scientists) is one of the greatest ways to learn science and to develop the pipeline of scientists and new developments. Yet funding for research that is not "big science" is becoming more difficult to obtain. This will have an impact on innovation and discourage increasingly more of our brightest youth from careers in science.

We are also falling behind as a science-literate society, which is even more troubling. We have a deep divide between those who understand technologic advances and those who don't. This leads to distrust and misunderstandings and, sometimes, to public paranoia about new technologies that could actually be extremely important to our future as a race, or as a planet. US taxpayers should be crying out because research is not supported in a competitive fashion, but they don't. That disturbs me more than seeing other countries gaining the upper edge in technology.

Diane Husic
Moravian College
Bethlehem, PA
dhusic@moravian.edu

Goodbye to LD50?

In "Goodbye to LD50?" ¹ you describe the recommendation of a Regulatory Toxicology and Pharmacology report that drug companies stop using the classic toxicity test to inform clinical trials. I believe that eliminating the LD50 test will deprive researchers of vital information concerning the safety and effects of newly created drugs. Critics may say that the physiology of rats and mice might be different from human physiology and therefore useless in extracting meaningful data, but that is not the purpose of an LD50 test. The LD50 test is used to determine the relative toxicity of a substance normalized to the variation of the animals' sizes. Knowing the toxicity of a substance compared to other known compounds enables researchers to extrapolate the dosage that could result in death for humans.

To say that the LD50 test is not relevant is like saying that the damage sustained by an insect from a marble dropped from 10 stories is not relevant to determining the damage that a human would sustain from that same marble. That is ludicrous. If the LD50 test is eliminated, another test, such as the Fixed Dose Procedure, must be used in its place to determine the toxicity of these drugs. Are the drug companies suggesting that we replace the rats with people?

Ron Fong
NASA
Moffett Field, CA
ronald.c.fong@nasa.gov

*The views expressed in this letter are those of Mr. Fong and do not reflect the views of NASA or anyone else in the organization.

Gene therapy conflicts

Re: "Fixing gene therapy trials," ¹ you note that the authors of a recent series of articles about informed consent in gene therapy trials were key players in the death of an 18-year-old in a 1999 gene therapy trial that had called into question informed consent. Though I appreciate being informed of this strikingly ironic example of the kinds of conflicts of interest that increasingly characterize medical research, I am not surprised. A system that uses ruthless competition oriented toward potentially gargantuan rewards could produce nothing else. While the appearance of moral and ethical restraint is valued, the actual practice is punished in service of a maniacal pursuit of wealth and fame. Science tolerates this situation at the risk of becoming just another source of ignorance and intrigue. False pride is worse than no pride at all.

Herb Ruhs
Pediatrician
Missoula, MT
hruhs@pacific.net

The errors made in the protocol in the unfortunate 1999 case were in the site and dosage of delivery, and changing the protocol on the fly is uncalled for by the tenets of good science, regardless of whether one is considering a gene therapy trial or a trial designed to determine one's preferred cola. The potential consequences of ad hoc changes in protocol are of course dire in the case of many clinical trials; however, clinical research has evolved for the better with Institutional Review Boards and systematic training of clinical researchers in the areas of ethics, experimental design, and regulatory matters. IRB approval of updates to protocols is required as a matter of routine.

Here we see scientists involved in the worst potential breach of ethics (or at best, sloppy science) writing an editorial calling for improvement over old practices. I find it refreshing: It is evidence that the objectivity that science expects of its practitioners is alive and well, and that science is a self-correcting discipline. I see the motives of the editorial as pure and worthy of reading by every first-year resident.

Imagine how damaging it would have been, by comparison, for these authors to spend countless hours writing editorials defending their practices.

James Lyons-Weiler
Allison Park, PA
Missoula, MT
jameslyonsweiler@yahoo.com