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CLINICAL REVIEW:
David J Weatherall
Science, medicine, and the future: Single gene disorders or complex traits: lessons from the thalassaemias and other monogenic diseases
BMJ 2000; 321: 1117-1120 [Full text]
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Rapid Responses published:

[Read Rapid Response] Rectifying distortions in the New Genetics
Richard Fielding   (6 November 2000)
[Read Rapid Response] thalassemia and sickle cell anemias
Mara Raidy   (10 November 2000)
[Read Rapid Response] The safe use of Placental Umbilical Cord whole Blood Transfusion in Patients Suffering from anemia and Thalassemia in underresourced regions of the World
Niranjan Bhattacharya DSc, MBBS, MD, MS, FACS(USA), Maity C.R.,Mukherjee K.L.,Chettri M.K.,Bhattacharya S,Bhattacharya M, Pal S, Sen G, Biswas T, Bandopadhyay T,Upadhyay S, Halder N.K, Ghosh M, Chatterjee M   (9 June 2004)
[Read Rapid Response] no room for evolution
Alfred N Jackson   (9 October 2004)

Rectifying distortions in the New Genetics 6 November 2000
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Richard Fielding,
Senior lecturer
Department of Community Medicine, HKU, Hong Kong.

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Re: Rectifying distortions in the New Genetics

Sir, How we think about cause in disease is often too simplistic (though it promises to make lots of people rich). If medicine is ever to break out of the stalemate it faces regarding "chronic" disease such as cancer, it needs a change of focus. The genome may be an important piece, but it is only a piece in a very, very complex chess game. This imbalance is highly misleading and urgently needs correction. Weatherall's article is a first step. Please BMJ, more of the same!

References

1. Science, medicine, and the future: Single gene disorders or complex traits: lessons from the thalassaemias and other monogenic diseases
David J Weatherall. BMJ 2000; 321: 1117-1120

thalassemia and sickle cell anemias 10 November 2000
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Mara Raidy,
blood group dna research
BCE Institute

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Re: thalassemia and sickle cell anemias

Thalassemia is indeed a very complex genetic disorder.

It may be easier to investigate and cure sickle cell anemia, hemoglobin S.

The main defect in thalassemia, the lack of production of beta globin, results from different gene sequences in different populations

However, in sickle cell anemia, the single gene defect is the same in everyone who has that disease.

The safe use of Placental Umbilical Cord whole Blood Transfusion in Patients Suffering from anemia and Thalassemia in underresourced regions of the World 9 June 2004
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Niranjan Bhattacharya DSc, MBBS, MD, MS, FACS(USA),
Surgeon and Superintendent Bijoygarh State Hospital
Bijoygarh State Hospital, Calcutta700032,India,
Maity C.R.,Mukherjee K.L.,Chettri M.K.,Bhattacharya S,Bhattacharya M, Pal S, Sen G, Biswas T, Bandopadhyay T,Upadhyay S, Halder N.K, Ghosh M, Chatterjee M

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Re: The safe use of Placental Umbilical Cord whole Blood Transfusion in Patients Suffering from anemia and Thalassemia in underresourced regions of the World

Dear Sir, Thank you for publishing an interesting review on Science Medicine and the Future, etc., by David J Weatherall. While scientists working in centres of excellence are trying to unearth the genetic complexity and clinical diversity of thalassemic presentation, the bread and butter of the treatment in under-resourced countries remains the long cherished demand for a safe transfusion and an arrangement to treat iron abuse with chelation and other basic support medicine.Even this is extremely difficult in many countries of Sub-Saharan Africa ,certain regions of Latin America and South Asia in particular.We have got a suggestion which we want to narrate here.

In the animal kingdom, even herbivorous animals swallow the placenta after the birth of their baby (for example, the cow). In the human system, we do not know about the proper utilization of the placenta and membranes although there are suggestions regarding this on the basis of research on placental umbilical cord blood stem cells as an alternative source to bone marrow transplantation.The CD 34 stem cells constitute .01 percent of the nucleated cell compartment of the cord blood, the rest 99.99 percent of the cord blood is discarded.

In Bijoygarh State Hospital, Calcutta, India, we do not discard this precious gift of nature. In our earlier publications on placental umbilical cord whole blood transfusion, we wanted to examine the safety aspect of other components of cord blood transfusion, viz., fetal RBC, growth factors and cytokine filled plasma, etc., in different indications of blood transfusion, from the pediatric to the geriatric age group, in malignant and non-malignant disorders affecting our patients(1-4).

In the present (thalassemic) series we collected 64 units or umbilical cord whole blood aseptically from the umbilical vein after caesarean section in standard pediatric blood transfusion bags,* after the removal of the baby from the operative field and after confirming the stable condition of the mother. The volume of cord blood varied from 56ml. to 132ml. with mean 82ml ±16ml SD.

The cord blood was transfused immediately (within three days of collection) to 12 patients from 2 years to 28 years of age, from 1 April 1999 till date, after taking adequate consent and following the precautions of standard blood transfusion protocol. On the basis of the severity of clinical presentation the patients received 2 units to cumulative 25 units of blood within a span of 2years of initiating the present fetal hemoglobin rich cord whole blood transfusion. All the patients tolerated the procedure well ,there is rise of fetal hemoglobin proportionate to the amount of transfusion and in addition there is a sense of well being among the recepient of the cord blood. There has not been a single case of immunological or non immunological reaction in this series of transfusion so far.

Thalassemia consists of a group of disorders that may range from a barely detectable abnormality of blood, to severe or fatal anemia. Adult hemoglobin is composed of two alpha and two beta polypeptide chains. There are two copies of the hemoglobin alpha gene (HBA1 and HBA2), which each encode an alpha-chain, and both genes are located on chromosome 16. The hemoglobin beta gene (HBB) encodes the beta-chain and is located on chromosome 11. In alpha-thalassemia, there is deficient synthesis of alpha -chains. The resulting excess of beta chains bind oxygen poorly, leading to a low concentration of oxygen in tissues (hyopoxemia). Similarly, in beta thalassemia there is a lack of beta chains. However, the excess of alpha chains can form insoluble aggregates inside red blood cells. These aggregates cause the death of red blood cells and their precursors, causing anemia. The spleen becomes enlarged as it removes damaged red blood cells from the circulation.

The problem of thalassemia can mostly be combated with risk free blood transfusion and tackling the problem of iron abuse with chelation.There are also supportive drugs (anabolic steroid) and some selective drugs like hydroxyurea etc which can help extend the life of fetal hemoglobin etc. There are more than 20 million births in India per year and cord blood contains 60-80 percent fetal hemoglobin. On the basis of our experience with 64 units of placental umbilical cord whole blood transfusion in different varities of clinical presentation in anemia and thalassemia (within three days of collection and preservation, at 1-60C, in a refrigerator), we are of the opinion that this is a safe transfusion protocol, which takes advantage of the safety of nature’s finest biological sieve, i.e., the placenta, as an alternative to adult whole blood transfusion.It also has the advantage of a higher oxygen carrying capacity of fetal hemoglobin in addition to many growth factors and other cytokine filled cord blood plasma along with its hypoantigenicity(5-8) and the metabolic advantages of neonatal or cord blood .

* Pediatric blood bag contains 14ml. anticoagulant – Citrate Phosphate Dextrose Adenine solution USP and a 16g needle for transfusion.

References:

1) Bhattacharya N, Mukherjee KL, Chettri MK, Banerjee T, Mani U, Bhattacharya S, “A Study Report of 174 Units of Placental Umbilical Cord Whole Blood Transfusion in 62 Patients as a Rich Source of Fetal Hemoglobin Supply in Different Indications of Blood Transfusion”, Clinical and Experimental Obstetrics and Gynecology, vol.28, no.1, 2001 : 47-52.

2)Bhattacharya N, Bandopadhyay T, Bhattacharya M, Bhattacharya S, “Do Not Discard 99.99% of the Human Placental Umbilical Cord Blood for the Sake of Stem Cells Only”, bmj.com, 6 Oct. 2001, Rapid Response to Proctor SJ et al, “Umbilical Cord Blood Bank in UK”, Editorial, BMJ, 2001, 323: 60 -1.

3) Bhattacharya N, Bandyopadhyay T, Bhattacharya M, Bhattacharya S, “Immunization and Fetal Cell /Tissue Transplant : A new strategy for geriatric treatment 6th April 2002, rapid response to Gott lieb S” Drug effects blamed for fifth of hospital death among elderly BMJ, 2001; 323 : 1025 b

4)Bhattacharya N et al, “Umbilical Cord Whole Blood Transfusion : A Suggested Strategy to Combat Blood Scarcity in Ireland”, Rapid Response to Payne D, BMJ.com, 324 (7330), Jan. 2002: 134.

5)Bhattacharya N, Chhetri MK, Mukherjee KL, Ghosh AB, Samanta BK, Mitra R, Bhattacharya M, Bhattacharya S, Bandyopadhyay T, “Can human fetal cortical brain tissue Transplant (upto 20 weeks) sustain its metabolic and oxygen requirements in a heterotrophic site outside brain ? A study of 12 volunteers with parkensons disease, Clinical and Experimental Obstetrics and Gynaecology, Vol-29, No. 4, 2002

6)Bhattacharya N, Chhetri MK, Mukherjee KL, Das SP, Mukherjee A, Bhattacharya M, Bhattacharya S, “Human Fetal adnenal transplant : A possible role in relieving intractable pain in advanced rheumatoid Arthritis, Clinical and Experimental Obstetrics & Gynaecology, vol. 29, No. 3, 2002 .

7)Bhattacharya N, Mukherjee KL, Chettri MK, Banerjee T, Bhattacharya S, Ghosh AB, Bhattacharya M, “ A Unique Experience with Human Pre-immune (12 weeks) and Hypo-immune (16 weeks) Fetal Thymus Transplant in a Vascular Subcutaneous Axillary Fold in Patients with Advanced Cancer: A Report of Two Cases”, European Journal of Gynecological Oncology, vol.22, no. 4, 2001 : 273-7.

8)Bhattacharya N, “Fetal Tissue/ Organ Transplant in HLA Randomized Adult’s Vascular Subcutaneous Axillary Fold: A Preliminary Report of 14 Patients”, Clinical and Experimental Obstetrics and Gynrcology, 2001; 28(4); 233-239.

Competing interests: None declared

no room for evolution 9 October 2004
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Alfred N Jackson,
primary care physician
bulawayo zimbabwe

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Re: no room for evolution

The theory of evolution has,until relatively recently,been promoted mostly via dissertations involving the evidence of fossilised remains together with various postulates based on the relatively recently acquired knowledge of genetic composition and expression,knowledge about nucleotide sequencing/coding/transcription and various surmised mechanisms of mutation.In addition to this a great deal of thought has been given to the phenomena which affect populations of organisms and their interactions,and this whole field of ecology and ecosystems etc.has received substantial attention,and much of the knowledge on this subject has been variously invoked in the process of formulating and revising and teaching and publicising the theory of evolution.

My own experience was grounded in the controversies surrounding the theory of evolution.And I often wondered about the possibility of a link between chromosome numbers and the surmised evolutionary"genealogy".After all,I thought,since evolution is so closely associated with genes and mutations and inheritance and selection,it would be more rational to take a closer look at chromosome numbers than at fossilised skeletal remnants and radiocarbon traces.Now it is impossible,I suppose,to obtain genomic material from fossils,but we should be able to correlate chromosome numbers with the surmised evolutionary relationships based on increasing orders of complexity,comparative anatomy and physiology,and so forth.

Chromosome numbers were not easy to find.So I was delighted when I discovered www.kean.edu/~breid/chrom2.htm .You can imagine my surprise at the information on this website-chromosome numbers which did not correspond in any conceivable fashion with the evolutionary hierachical order.

Another discovery related to the mechanisms of meiotic cell division(the first and vital step in sexual reproduction).Since synapsis of homologous chromosomes requires a certain degree of homology between homologous chromosomes,and since meiosis(and gametogenesisand sexual reproduction)cannot proceed in the absence of synapsis between homologous chromsomes,it becomes exceedingly difficult to postulate how any new and different(i.e.different in number,at least)set of chromosomes could have appeared in any new and different organism in such a way as to be sexually reproducible.Sexual reproducibility would require the appearance of two new(and almost identical* )sets of homologous pairs of chromosomes(one set in each of a sexually reproducing couple).*[the synapsis of chromosome pairs in the gonads of the offspring would demand a degree of homology between the respective pairs of chromosome pairs in the parents].

If there are any persons who consider it at all feasible to attempt to postulate how the requirements of meiosis could have accomodated an evolutionary chain of ancestry which resulted in the chromosome numbers listed at www.kean.edu/~breid/chrom2.htm their postulations would make fascinating reading.Almost as fascinating as would be an account of the evolution of the haemoglobin molecule-it's evolution from the beginning,that is.Because the ever pressing need for oxygen would not allow much time for evolution.

Competing interests: None declared