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"It is virtually useless to search for single factors as causes of complex diseases or to ascribe cause-effect relationships by simple, isolated, biochemical mechanisms." Hormones in milk Re: "What's in your milk?"1 Although Ron Kensinger claims that pasteurization reduces IGF-1, the opposite has been found.2 In addition, there is a huge difference in the ability of the body to regulate endogenous chemical signals compared to those which are foreign. There is a c

The Scientist Staff
Apr 1, 2007
"It is virtually useless to search for single factors as causes of complex diseases or to ascribe cause-effect relationships by simple, isolated, biochemical mechanisms."

Hormones in milk

Re: "What's in your milk?"1 Although Ron Kensinger claims that pasteurization reduces IGF-1, the opposite has been found.2 In addition, there is a huge difference in the ability of the body to regulate endogenous chemical signals compared to those which are foreign. There is a chronic and cumulative effect on growth hormone signalling and a threshhold level that is differentially set for different people. Hormones - by virtue of their purpose - have large effects in small quantities, and sometimes it is the smaller quantities that have a greater influence due to the lack of negative-feedback they'd produce.

Shirin Kalyan, PhD
Division of Endocrinology, Faculty of Medicine
Univeristy of British Columbia
shirinka@hotmail.com

References

1. I. Oransky, "What's in...

My laboratory has investigated the question of dairy protein and experimental cancer development since the 1960s and we have shown, in dozens of publications in top journals,1-3 that reductionist research findings are more than likely to be very misleading. It is virtually useless to search for single factors as causes of complex diseases or to ascribe cause-effect relationships by simple, isolated, biochemical mechanisms.

For example, we showed in extensive studies that casein, the main protein of cow's milk, increases cancer development by an entire spectrum of 'explanatory mechanisms' - increased cell replication in the target tissue harboring the cancer, increased formation of chemical carcinogen-DNA adducts, increased cellular uptake by carcinogens, repressed formation of cancer inhibiting natural killer cell activity, increased endogenous formation of IGF, increased expression of oncogenic genes, increased formation of circulating estrogen, etc., etc. Moreover, we could reverse cancer development--forwards or backwards--by intervention with modest changes in casein intake. My son and I also published a book on the subject.4

T. Colin Campbell
Cornell University
Ithaca, New York
tcc1@cornell.edu

References

1. T.C. Campbell, "Chemical carcinogens and human risk assessment," Fed Proc, 39:2467-84, 1980. 2. T.C. Campbell, et al., "Non-association of aflatoxin with primary liver cancer in a cross-sectional ecologic survey in the People's Republic of China," Cancer Res, 50:6882-93,1990. 3. L.D. Youngman, T.C. Campbell, "Inhibition of aflatoxin B1-induced gamma glutamyl transpeptidase-positive (GGT+) hepatic preneoplastic foci and tumors by low protein diets: evidence that altered GT+ foci indicate neoplastic potential," Carcinogenesis, 13:1607-13, 1992. 4. T.C. Campbell, T.M Campbell, The China Study. Startling Implications for Diet, Weight Loss and Long-Term Health, Benbella Books: Dallas, 2006.

Kalyan's suggestion that pasteurization increases IGF-1 is incorrect. The reality is that humans secrete endogenous IGF-1 in their GI tract in large mass relative to the potential milk source.1 Drinking three glasses of milk per day would equate to <3% of endogenous secretions into the GI tract.

While I generally agree with Campbell that the whole food studied in vivo is the "complete package," the confounding effects are vast and difficult to interpret. While rodent studies are less confounded due to low animal to animal variation and control over the diets, the extrapolation or direct testing in humans with their large genetic variation and very diverse diets suggests unknowns in data interpretation.

I agree that that excellent nutrition is the basis of good growth and, if a cancer is present, accelerated cancer growth. Our better nutrition is a contributor to longer life expectancy, and longer life increases disease risk. Milk has been known to be an excellent nutritional source of proteins, calcium and specific vitamins and minerals.

Craig Baumrucker
Penn State University
University Park
crb@psu.edu

References

1. S.H. Kang et al. "The effects of dairy processes and storage on insulin-like growth factor-I (IGF-1) content in milk and in model IGF-1-fortified dairy products," J Dairy Sci, 89:402-9, 2006.

Avoiding conflict in the lab

A principal investigator can avoid a lot of conflict by having a lab manager.1 Having what you need at your fingertips can assuage a lot of angst in the lab. A lab manger or lead technician brings continuity into the lab and helps conserve valuable resources. It also helps keep the most senior scientists in the group from playing a technician's role in lab, which can lead to resentment and loss in productivity. I work closely, in a supportive role, with the research scientists and can spot trouble brewing more quickly than can the PI. I am also always available to lend a hand or an ear. Sometimes, my excitement over an experiment's progress is just what a scientist needs.

Sue Sipkovsky
Michigan State University
sipkovs3@msu.edu

To avoid bad blood in the lab over authorship issues, Susan Parkhurst advises us to establish authorship guidelines in the lab and to be consistent with the application of these guidelines to authorship decisions.1 According to Parkhurst's advice, individual labs could have different authorship rules: in one lab, for example, technicians might receive authorship credit, whereas in another, they would always be excluded from authorship. I consider this quite perilous, and would like to give a different advice: Labs (and research journals) should adhere to uniform authorship guidelines such as those established by the International Committee of Medical Journal Editors (ICMJE).2,3

If labs adhered to these guidelines, the only criterion for authorship decisions would be the scientific contribution lab members have made to a given project. The professional status of lab members would not need to be considered nor the amount of time invested in the project by each of the lab members, and it would also not matter whether a lab member had left the lab before completion of the study.

Regina Goetz
Department of Pharmacology
New York University School of Medicine
goetz@saturn.med.nyu.edu

References

1. K. Grens, "Dealing with conflict," The Scientist, 21(2):26-32, February 2007. 2. International Committee of Medical Journal Editors, "Uniform requirements for manuscripts submitted to biomedical journals", N Engl J Med, 324:424-8, 1991. 3. D. Riesenberg, G.D. Lundberg, "The order of authorship: who's on first?", J Am Med Assoc, 264:1857, 1990.

Peering into Carnegie

In "Peering into Carnegie"1, Alejandro Sanchez Alvarado claims that "research on the flatworm largely ceased after Thomas Hunt Morgan abandoned the organism in 1910." On the contrary, the planarian literature has been quite extensive since then. L.H. Hyman of the American Museum of Natural History published extensively on planarians between 1919 and 1951. Between 1945 and 1985 several books and hundreds of papers about planarians were published in English, French, Italian, Japanese, and German.2,3 My own work between 1965-1978 showed that planarians were an excellent system to demonstrate the role of stem cells (neoblasts) and their kinetics in (1) the mechanism of aging, (2) the quantitative relationship between the slope and intercept of the radiation survival curve for neoblasts and the slope and LD50 for the animal's survival, (3) the nature of teratoma-like tumors resulting from misdirected differentiation of stem cells and (4) with my student V.E. Steele, that anterior:posterior polarity is determined by the bio-electrophoresis, from head to tail, of a highly electronegative protein which inhibits differentiation of neoblasts into brain tissue. This last point explained polarity reversal by externally applied electrical fields, frog forelimb regeneration after sciatic nerve rerouting, and the acceleration of bone healing in humans.

Christopher S. Lange
SUNY Downstate Medical Center
Brooklyn, NY
clange@downstate.edu

References

1. B. Maher, "Peering into Carnegie," The Scientist, 21(2):49-53, February 2007. 2. H.V. Bröndsted, Planarian Regeneration, (International series monographs in pure and applied biology. Zoology Division), Vol. 42, Pergamon Press: Oxford, 1969. 3. C.S. Lange, "Stem cells in planarians" Chapter 3 pp 28-66, In Stem Cells. Their identification and characterization, (Ed. C.S. Potten), Churchill Livingstone: London, 1983.

Pharma Goes Hollywood

Re: "Why Pharma Must Go Hollywood."1 Six Sigma does work effectively in R&D - only when properly applied. It's mostly useful in improving the repeatable parts of R&D activity, which frees people's time and attention for higher value work, and for improving trust and reliability in product designs, which enables Six Sigma manufacturing performance. Pharma is a slight distortion because much of it already performs better than the 'one failure in 3.4 million tries' that Six Sigma shoots for. Improvement is still possible by making scientists aware of strong parallels between Six Sigma improvement approaches and scientific method, as well as by carefully managing the involvement of those who don't understand scientific method in R&D improvement initiatives. Learn about Six Sigma in R&D at www.iriinc.org.

Albert Johnson
Corning Incorporated
Corning NY
JohnsonAL@Corning.com

References

1. L. Bernal, "Why pharma must go Hollywood," The Scientist, 21(2):42-7, February 2007.

Not only does this high-ranking industry executive confirm some critics' analysis that the real cause of the dearth in pharmaceutical innovation has nothing to do with overconcern with drug safety, but he points to the real culprits: the maturing of the industry (to use his phrase, "the low-hanging fruit" has been picked problem) and an internal culture that doesn't reward good science or focus on medical need. Now, how do we get someone like him to go public? There's going to be a lot of hearings around FDA reform legislation this year. It would be nice if someone from Big Pharma told these truths rather than sling the trade group's sterile PR.

Merrill Goozner
Silver Springs, MD
Merrill@goozner.com

'Shroom science

Re: Shroom Science.1 As explained in the Psychopharmacology study2, the use of methylphenidate as an active placebo was a deliberate decision made for sound methodological reasons. The issue was one of preserving the integrity of the double-blind in the study in order to control for expectancy effects. In four commentaries simultaneously published with the study, several distinguished researchers praised the wisdom and effectiveness of using methylphenidate as a control substance. Its mild physical symptoms were so effective and effects that could be mistaken for the influence of psilocybin that a full 23% of the double-blind placebo sessions were mistaken by the trained session monitors for psilocybin sessions. In most of those, methylphenidate sessions were mistaken for psilocybin sessions. This is one of the conspicuous triumphs of the study.

Beyond this, the suggestion that drug research in any way explicitly or implicitly implies an equivalence of safety and efficacy between the test compound and comparison substance is absurd.

Finally, the author's contention that this study did not receive much media attention is simply false. This study was not only covered in a detailed piece by the Associated Press, but independently covered by dozens of media outlets including The Wall Street Journal, The Economist, and CNN.

Barnaby Thieme
Associate Editor
Erowid.org
bathieme@hotmail.com

References

1. G. McGee, "Shroom science; Safe and effective?" The Scientist, 21(2):24, February 2007. 2. Griffiths, RR, Richards WA, McCann U, Jesse R. "Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance." Psychopharmacology (Berl.), 187:268-83, 2006

The idea that the public will be influenced by the implication that mushrooms are "as safe" as Ritalin when the two are used in studies together falls apart when you consider that in the 1960's, all sorts of "scientific" research came out in the popular press about how dangerous psychedelics were (chromosome damage and the like). All this alarmist research (refuted later by more precise unpublicized research) failed to prevent the use/abuse of psychedelics by the public.

Douglas R. Fraser
London
dr.fraser@gmail.com

Glenn McGee responds: I have been overwhelmed by the rage expressed by those who have offered commentary on the article. My point, which seems to me hardly debatable, is that this is interesting and good science, conducted by good scientists, with great potential, but that history teaches that if we are not very careful about how the studies are designed and constructed, there is the potential for needless risks on the part of the public.

I'm not an opponent of the research. I can see that there are scientific issues I edge up against when I complain only of one particular issue in the Hopkins study, which I suggest may be "sending the terribly premature message that the two substances are in any sense equivalent in terms of effect or safety." The point was that unless you have been asleep the last 10 years, you know that there is a huge literature about enhancement uses of Ritalin and other similar drugs, and that the comparison of psilocybin to a compound that is oft utilized in that way was undesirable if it is important to the researchers at Hopkins not to become fodder for lengthy articles about "researchers pushing a new form of enhancement."

The fact that those articles haven't been written yet, no matter what my critics helpfully uncovered in finding story after story about the fact that there was a study at Hopkins, is indeed a blessing. And I hope that those who share my view that this research is important will try to not only read my column for what I actually said, but also to see the debate on this page for what it actually is - a dangerous desire to mow over anyone, in the name of keeping the ball rolling.

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