Stem Cells Cure Sickle Cell Anemia In Mice

Last week’s Scienceonline (December 6 2007) had a most instructive report by American scientists, Timothy Townes, Rudolph Jaenisch, Jacob Hanna, and others from the University of Alabama and Massachusetts Institute of Technology’s Molecular Biology Department. They proved that mice that had been genetically modified in the laboratory to develop sickle cell anaemia can be made to produce embryonic stem cells from cells collected in the skin of their tails. Embryonic stem cells are known to be capable in later life of developing into any of different tissues. These so-called induced pluripotent stem cells (IPS cells) were then made to produce healthy haemoglobin by replacing the defective beta-globin sickle cell gene (S) with normal adult gene producing haemoglobin-A (nothing to with Blood Group A!). These were then injected into similar mice with sickle cell anaemia and, lo and behold, normal adult haemoglobin was produced and the mice improved clinically.

            So far so good news, but the cautionary tale is this: it needs the help of retroviruses to shift the genes around to give the required result, and where did you last hear of retroviral activity? AIDS, of course and as one of the scientists put it: “We need a delivery system that does not integrate itself inside the genome. Retroviruses can disrupt genes that should not be disrupted or activate genes that should not be activated”.

            If skin cells of mice can be made to behave like embryonic cells which obey orders given them to produce this or that, the next question is this: “Can human skin cells from sickle cell anaemia patients be similarly programmed to this end?” We can’t wait, though we know that transplanting induced pluripotent cells carry a high cancer risk, not to mention the effect of the high dose of X-rays required to destroy the faulty blood cells in the body before the new ones are planted.

Two more comments:

(i) How much would a New Yorker pay for the procedure, if it proved successful in humans? Cost itself should not disqualify a process that would abolish pain, but one needs ask the question. Until persons producing inherited ‘ACHEACHE’ haemoglobin begin to be able to produce acquired ‘NORMNORM’ or ‘NORMACHE’ haemoglobin through IPS cell manipulation, we need to pursue the public health measures that I have been stressing for preventing crises, and we must continue urging on our kith and kin genetic counselling with voluntary family size limitation [Konotey-Ahulu FID, The Lancet, 1 December 2007, volume 370, pages 1826-27: “Need for ethnic experts to tackle genetic public health”]       

(ii) A report by one Eric Bender in Cambridge Massachusetts (December 6 2007) began like this: “Mice with a human sickle cell anemia disease trait have been treated successfully…..” Now those familiar with this website know that there is no such thing as “sickle cell anemia disease trait”. There just isn’t! While sickle cell anaemia is also sickle cell disease, sickle cell trait is NEITHER of these. Indeed, as the blog above shows, I was given four bodyguards in Philadelphia for stressing this very point, namely that SICKLE CELL TRAIT IS NOT SICKLE CELL ANAEMIA (SICKLE CELL DISEASE). Please read that blog above again, and turn to my FAQ [Frequently Asked Questions]. Even well educated professionals use the terms interchangeably. Remember this: Only sickle cell anaemia can be referred to as sickle cell disease because both have TWO ‘Ache’ genes. The Sickle Cell Trait has only one ‘Ache’ haemoglobin gene. Insurance companies have been known to blur the distinction and have over charged sickle cell traits (many of whom have won gold medals at Olympic Games, even at a height of 8,000 ft above sea level). How can persons who ran and beat the whole world be charged a greater premium for health insurance, than the people they beat at the games?   

Opiates for pain in dying patients and in those with sickle cell disease

Opiates for pain in dying patients and in those with sickle cell disease

Dorothy Logie and Mhoira Leng’s report of 6 October describes a conference in Nairobi which highlighted opiophobia – the fear of using morphine therapeutically – “as a big obstacle facing palliative care services in the (African) continent” [1]. The conference was concerned with dying patients. In his rapid response, however, Jecko Thachil concentrated on the use of opiates in sickle cell disease patients. He states that while “very high amounts of opiates (often in hundreds of milligrams) are often required for the patients who suffer from recurrent sickle crises” [2], the expected analgesic effect leaves much to be desired, not to mention side-effects. Dealing with terminally ill patients is one thing; opiate administration to sickle cell disease patients is something else entirely.

Dr Thachil feels an “increased need for additional education regarding sickle cell disease…” Has he examined the experiences of two physicians who personally supervised thousands of people with sickle cell disease on both sides of the Atlantic continuously for years? [3, 4] Treating sickle cell disease is not the same as managing the sickle cell disease patient [5]; the difference in the two approaches tending to separate haematologists on the one hand, from physicians and family practitioners on the other. When a white British consultant physician in a London teaching hospital complained that “the haematologists here have created a cohort of addicts” [6] a white consultant haematologist in another London teaching hospital tore strips off him, accusing him of being a racist for depriving suffering black patients of pain relief, an attack which made me respond thus: “White physicians who, at the risk of being misunderstood by (that haematologist), voice their displeasure at what they see happening on their wards deserve commendation, not condemnation” [7].

Not far from where Dr Jacko Thachil works, also on Merseyside, “during a ward round in a provincial teaching hospital with consultant haematologists on March 6, 1997, I was shown a woman who had been on continuous opiate infusion since September, 1996” [7]. I went on to say in my Lancet communication: “Far from the consultants taking umbrage because I pointed out that the patient could not have been in sickle cell crisis for 6 months, they were happy to discuss with me the way forward” [7]. Dr Thachil feels “an increased need for additional education regarding …addiction to pain medication…and treatment of pain” and he concludes “but who and where these should be focussed on is a matter for debate” [2].

Not a matter for debate at all in my opinion: May I suggest to him certain facts he might wish to probe in his quest for education?

(a) “In Jamaican experience ..morphia or its derivatives are rarely used or necessary” [8] How did Graham Serjeant achieve this?

(b) “Most painful crises may be treated in a day-care centre, the patient returning home in the evening” [9] How is this possible if hooked up on morphine or diamorphine pump “as in the recommended UK protocol”? [6]

(c) “We are convinced that the chest syndrome in the UK and the USA is not entirely unrelated to the routine use of opiates in those countries for sickle cell crises”. [10] Some nurses I am in touch with can write an MSc thesis on this.

(d) Goodman from the USA (where diamorphine is banned for patients) found the use of ketorolac in painful sickle cell crises as efficient as morphine but without the latter’s respiratory depression [11]. So why do British haematologists prefer to use morphine and diamorphine? Answer: “Ketorolac has no product licence in the UK for this indication” [12]

(e) Two questions that I have asked British Haematologists several times but which have never been answered, and which Dr Thachil may now ask the National Institute of Clinical Excellence (NICE) for help in answering:

(i) “Why do West African and West Indian patients with sickle cell disease who did without morphine in their countries have to be given morphine pumps during sickle cell crises when they come to the United Kingdom?” [6, 13]

(ii) If pain from whatever cause deserved the most potent analgesic, and dysmenorrhoea has been known to be intolerably painful, would a British haematologist “not consider it unwise for a hospital to administer diamorphine as routine management of young women?” [7]

Four encouraging signs have emerged in the UK since I have been voicing my displeasure at the use of diamorphine and morphine pumps for patients with sickle cell crises: (1) Some haematologists in the UK and the European continent have abandoned the practice in spite of what the ‘approved protocol’ displays in the emergency rooms. (2) Some sickle cell disease patients have become more vocal in their displeasure of the practice. To them ‘opiophobia’ is not to be condemned [1], but commended. (3) Some family practitioners are looking after their patients at home, using intravenous fluids and other than powerfully addictive opiates to help these patients instead of submitting them to hospital care. (4) A clearer grasp of the causes of crisis has put more emphasis on public health measures (fluids, warmth, treatment of infections, dressing properly, anticipating hazards, immunisations, avoiding tobacco and alcohol), enabling patients prevent crises and helping them use the excellent non-sickling genes they have inherited from their parents to achieve as much of their full potential intellectually as possible [10].

It is therefore not surprising to find that the sickle cell disease patients who have become lawyers, teachers, businessmen and women, nurses & midwives, pharmacists, and even doctors are those whose haematologists have abandoned the opiate culture. Occasionally, however, one found even professors of haematology who would defend the prescribing of diamorphine for a sickle cell disease patient with severe difficulty in breathing. “Chest syndrome” was always there to blame, if the patient died [6].

When in my genetic counselling and family size limitation (GCFSL) drive in Ghana and in the Ghanaian community here in the UK I sense that the urgency of my message is being glossed over I tell my fellow countrymen and women in plain language that if they continue to procreate at the rate they are doing, and more sickle cell disease (ACHE/ACHE) patients are born, the chances are that in the UK they may end up on a heroin drip. This concentrates the mind, and they listen to me. “One in three of you is a NORM/ACHE. Do you want to end up with ACHE/ACHE children who will be given heroin for pain?” [http://www.konotey- ahulu.com/diagram.asp]

Felix I D Konotey-Ahulu MD(Lond) DSc (UCC) FRCP DTMH FGA FGCPS FAAS FTWAS
Kwegyir Aggrey Distinguished Professor of Human Genetics, University of Cape Coast, Ghana and Consultant Physician Genetic Counsellor, Ten Harley Street, London W1N 1AA, England.

Conflict of interest: None declared

1 Logie D, Leng M. Africans die in pain because of fears of opiate addiction. BMJ 2007; 335: 685

2 Thachil J. The fear of opiate addiction – not unique to Africa. Rapid response BMJ 2007, 8 October.

3 Serjeant GR. Sickle cell disease. Oxford: Oxford university Press, 1992 (Second Edition)

4 Konotey-Ahulu FID. The sickle cell disease patient. London: Macmillan 1991; Waftord: Tetteh-A’Domeno Co, 1996.

5 Konotey-Ahulu FID. Sickle cell disease and the patient. Lancet 2005; 365: 382-383.

6 Konotey-Ahulu FID. Opiates for sickle cell crisis? Lancet 1998; 351: 1438.

7 Konotey-Ahulu FID. Opiates for sickle cell crisis. Lancet 1998; 352: 651-652.

8 Serjeant GR. Sickle cell disease. Oxford. Oxford University Press, 1985, page 204.

9 Serjeant GR. Sickle cell disease. Lancet 1997; 350: 725-730.

10 Ringelhann B, Konotey-Ahulu FID. Hemoglobinopathies and thalassaemias in Mediterranean areas and West Africa: historical and other perspectives 1910 to 1997. Atti dell’Accademia delle Scienze di Ferrara 1998; 74: 267-307.

11 Goodman E. Use of ketorolac in sickle cell disease and vaso- occlusive crisis. Lancet 1991; 338: 641-642.

12 Liesner RJ, Vandenberghe EA, Davies SC. Analgesics in sickle cell disease. Lancet 1993; 341: 188.

13 Konotey-Ahulu FID. Morphine for painful crises in sickle cell disease. BMJ 1991; 302: 1604.

Competing interests: None declared

Link : http://www.bmj.com/cgi/eletters/335/7622/685#177986

There is nothing mysterious about kwashiorkor

There is no mystery [1, 2] about “kwashiorkor”, which is a word from a Ghanaian tribe, my very own Krobo/Dangme/Ga megatribe [3, 4]. Indeed, it was when I was a toddler that the remarkable white woman based at the Princess Marie Louise Hospital in Accra (before the Gold Coast became Ghana) first described the condition which was brought to her attention by my fellow tribes folk [5,6].

Imagine my utter astonishment when, coming over to England to read Medicine in London University, I heard Lecturer after Lecturer state with unwarranted confidence that “kwashiorkor means red hair in an African language”. The word means no such thing in my tribe. Kwashiorkor, as I once pointed out to a British Professor of Paediatrics in this very medical journal “is, primarily, a sibling positional word, which requires careful explanation to the non-native” [3]. It is a reflection of the 'birth position' of the sufferer, before it is a pathology [4], a fact emphasized by Dr Cicely Willams whose descriptions of the condition have not been bettered by anyone [5, 6, 7, 8].

Apart from being a Krobo tribesman, I have a further reason for claiming that I know more about Kwashiorkor than all the non-Ghanaian experts that have written volumes about the syndrome (Cicely Williams excepted). And I say that for this reason: In my tribe, it was said of me (the second child) the day my younger brother was born while I was not yet completely weaned – “afor ese kwasiorkor” [3] which, literally means “it has been born after him kwasiorkor”, stressing my positional risk of being sandwiched between my elder brother, Agbetey, who was just 13 months older than me, and the just arrived sibling who was also just 17 months my junior. See http://www.konotey-ahulu.com/images/generation.jpg for the first 3 children of my parents Rev & Mrs Konotey-Ahulu in Generation VII, and note how closely spaced we were.

The whole tribe expected me to develop kwashiorkor because of the birth of my brother. “The reason I escaped the syndrome first described by Dr Cicely Williams [3, 4] was simply because my educated parents took the same steps that Professor Marsden described from Brazil [9]: I was fed with beans, eggs, milk, minced meat, and Ovaltine” [3]. Less fortunate relatives of my age in my tribe, whose parents also had 3 children in less than 3 years, “and of whom it was also said 'afor ese kwasiorkor' went on to develop kwashiorkor because they could only afford to be fed with maize products such as akasa and k enky” [3].

I went on to make the point that: “The sibling positional word became almost invariably associated with the syndrome Cicely Williams was investigating, and although the term kwashiorkor was occasionally attached to a child who never went on to get the disease ” (just as in my own case), whenever the the syndrome kwashiorkor was seen in a child there was, more likely than not, very close proximity to a younger sibling” [3]. Exceptions, of course, occurred, “when children were orphaned” (as would be the case in Malawi ravaged with AIDS), regardless of sibling positioning, or multiple births. Indeed, I described such children (with photographs) on my AIDS tour of African countries [Ref 10 – See Figure 6.14, page 124]. I also described in a man who was mistaken for suffering from HIV-AIDS [Ref 10, photographs on pages 80-82] what has been called the Adult Kwashiorkor syndrome “in which diarrhoea, pitting oedema, hepatomegaly, dermatopathy, mental apathy, and hair changes result from protein energy malnutrition as, for example, in the creatorrhoea and steatorrhoea of severe alcoholic chronic pancreatitis”. This syndrome was completely reversible in the man described [10] when his alcoholism [he was on one litre and half of gin a day] was treated, diabetes reversed, pancreatin supplied, and protein supplements given [See remarkable change in just 6 months – Ref 10]. Should we have spent research funds finding out how much antioxidants this man's diet contained?

I had the enormous privilege of meeting up with 93-year old Dame Cicely Williams in Oxford in 1986 when we were photographed together[See The Lancet, Ref 4 for what she looked like at 93!]. I thanked her profusely for all that she did in my tribe in those colonial days wihout electron microscopes and sophisticated analysers. We both were greatly baffled why many of today's experts (especially those who have little experience of a tropical sojourn)find it difficult to accept that “Kwashiorkor is the result of a social pathology before it is the outcome of a biochemical pathology” [4]. Clinical epidemiology ie answering the questions Who? Which? Where? When? Why? What? and How? is far and away the best tool to investigate a tropical phenomenon such as kwashiorkor, and Cicely Williams gets my Full Marks for employing that tool with hardly any funds for medical research.

I repeat what I said a decade or so ago in The Lancet: “Those of us who grew up in the kwashiorkor belt and who have also had the benefit of an excellent medical education cannot but caution our ministries of health and social welfare about the danger of missing the social pathology wood for the trees of free radicals and leukotrienes”.

Nothing to declare, except that Kwashiorkor is my tribal language.

References

1 Fuchs GJ. Antioxidants for children with kwashiorkor. Brit Med J 2005; 330: 1095-1096.

2 Ciliberto H, Ciliberto M, Briend A, Ashorn P, Bier D, Manary M. Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial. Brit Med J 2005; 330: 1109-1111.

3 Konotey-Ahulu FID. Kwashiorkor. Brit Med J 1991; 302: 180-181.

4 Konotey-Ahulu FID. Issues in kwashiorkor. Lancet 1994; 343: 548.

5 Williams CD. A nutritional disease of childhood associated with a maize diet. Arch Dis Child 1933; 8: 423-8.

6 Williams CD. Kwashiorkor – a nutritional disease of children associated with a maize diet. Lancet 1935; 2: 1151-52.

7 Williams CD. Kwashiorkor. JAMA 1953; 1280-85.

8 Williams CD. Social Medicine in Developing Countries (Millroy Lecture, Royal College of Physicians). Lancet 1958; 863-66.

9 Marsden PD. Kwashiorkor. Brit Med J 1990; 301: 1036-37.

10 Konotey-Ahulu FID. What Is AIDS? T-A'D Co. Watford 1996.

Competing interests: None declared

Source Link as http://www.bmj.com/cgi/eletters/330/7500/1095#106854 14 May 2005

The perils of unmasking scientific truths

BMJ  2007;335:210-211 (28 July), doi:10.1136/bmj.39268.553021.47

Views & reviews

Personal views

The perils of unmasking scientific truths

Felix I D Konotey-Ahulu, consultant physician

London W1N 1AA

felix@konotey-ahulu.com

To be chosen to deliver the keynote address at the Martin LutherKing Jr Foundation's award banquet took me completely by surprise—andto find that four bodyguards had been assigned me shook me rigid.Nobel laureates Linus Pauling and Max Perutz, along with HermannLehmann, Roland Scott, A C Allison, Graham Serjeant, and I,were among a select few invited to Philadelphia to receive anaward “for outstanding research in sickle cell anaemia.” Butwhy was I asked to deliver the keynote address, with Paulingand other abnormal haemoglobin heavyweights on the platform?

Was it, perhaps, because a foundation commemorating a blackperson wanted to “show off” the only black African among thosereceiving the award? Was it, perhaps, because I was then directorof the largest sickle cell disease clinic in the world? Or wasit because I was the only person to have traced hereditary diseasein his forebears, with named patients, generation by generationback more than three centuries? Or was it the statement madea few weeks back in New York by Professor Helen Ranney of theAlbert Einstein University College of Medicine: “There is nosingle clinical experience in the United States comparable tothat of Dr Konotey-Ahulu”?

Such “perhaps hypotheses” competed in my brain when I arrivedin Philadelphia, that day in 1972. I walked out of the hotelto post a letter to my wife in Ghana. Just as I was about tocross a road, I heard a voice behind me: “Doctor! Doctor!! DoNOT cross that road. Where are you going?” The hugely builtAmerican (black) took the letter from me before dropping thebombshell: “I am one of your four bodyguards.”

The award organisers, who came within minutes of my call, explainedthat the text of my lecture alerted them to several problems.I had distinguished between sickle cell trait and sickle celldisease (sickle cell anaemia) because the terms were being usedinterchangeably, with disastrous consequences, by people whoshould know better. People with the trait (one abnormal gene)cope better than people with two normal genes with falciparummalaria, which kills sickle cell disease patients (two abnormalgenes) quicker than people with two normal genes. I had questionedpublished work which claimed that black Army recruits exercisingat an altitude of 4000 ft collapsed and died because of sicklecell trait. I had asked: “How could black sickle cell traitsrun and beat the whole world at the Olympic Games at MexicoCity, at an altitude of 8000 ft (double the altitude at whichpeople with sickle traits had been said to perish)?”

Why did I need four bodyguards? The award organisers thoughtI needed protection because I used data from an article by JamesBowman, who had named seven insurance companies in the UnitedStates which loaded the premium of black people with sicklecell trait, thus making lots of money on healthy people, whoneeded to pay 150% for health insurance. I explained that insouthern Ghana, where one person in five has the sickle celltrait, one in five sudden deaths in adults from whatever causewould be in people with sickle trait. Moreover, to make insurancerecommendations for only “black” sickle cell trait, withoutmention of “white” sickle trait in people from Greece, Cyprus,Turkey, India, and Saudi Arabia—many of whom lived inthe United States—was not medical science.

The award organisers advised me to leave names of the insurancecompanies out of my lecture. Even so, they could not run therisk that I would be bumped off before the lecture. I cannotremember being able to eat anything at the banquet, but I wasglad to be able to shake hands later with the great and good.I left Philadelphia immediately afterwards—no sight seeingfor me.

How dangerous is it these days to stand firm for scientifictruth—or rather, how risky is it to criticise scientificuntruths? The Ghanaian herbalist Nana Drobo was found with bulletholes in his head, not long after successfully treating a dyingFrench man with AIDS who was sent to him from the Ivory Coast.And how safe is it to point out that some of the prescribedprotocols for global malaria control are not the best answerto the problem? How many bodyguards would be adequate protection,when huge amounts of money are at stake in global health protocols?Money in itself is not sinful—rather, as it says in theBible: “The love of money is the root of all evil.”

Published : BMJ [www.bmj.com]

Heart Attack in sickle-cell disease and possible role of alcohol and over-transfusion?

Sickle-cell anaemia, “SS”, is just one of the 4 common phenotypes comprising sickle-cell disease, defined as possession of 2 globin gene variants at least one of which is the sickle gene.1 The others are sickle-cell Haemoglobin C disease, “SC”, sickle-cell beta-thalassaemia, “Sβ-Thal”, and sickle-cell hereditary persistence of Fetal Haemoglobin, “SFhereditary”. Ghana abounds in beta globin gene defects (qualitative and quantitative), which allowed me to study the clinical epidemiology of these 4 common phenotypes contemporaneously.2 For non-technical readers I use the term AcheAche for Sickle Cell Disease in all its forms, ie the possession of an ‘Ache’ gene from both father and mother.

Dr Pavlü and colleagues wrote an article about a 50 year old lady (Jan 20 2007, p 246)3 which is inadvertently misleading because although sickle cell anaemia ‘SS’’ (which their patient has) is sickle-cell disease, not all sickle cell disease is sickle cell anaemia. In over one thousand consecutive sickle cell disease patients that I have personally followed up, although ECG changes occurred frequently during sickle crises in all 4 phenotypes it is my “impression that signs of acute coronary occlusion and myocardial infarction, reversible after crisis, are more a feature of Hb SC disease where blood viscosity is greater than Hb SS disease (Figs 25.4 and 25.5; Case Histories 84 and 85)”.2   

     One reason their 50-year-old woman developed myocardial infarction could be because of increased red cell mass from “intermittently needed exchange transfusion”.3 What was the low-level haematocrit that determined need for transfusion, and what was the upper level attained afterwards? In my opinion the 110 g/L Hb level that many haematologists in the UK and USA feel “SS” patients required for their steady state does more harm than good1 2 4. I have both a sickle-cell anaemia (“SS”) patient who required to be bled to keep Hb level below 90 g/L otherwise he had thrombotic episodes2 (Case history 21, page 482) and a “Sβ-Thal” adult whom I once sent to Professor Lucio Luzzatto for a second opinion, and who demanded periodic venesections (removal of blood) to get Hb level below 850 g/L to abort incipient sickle crisis. Therefore, when was this 50-year-old last transfused before her myocardial infarction? What was her serum Ferritin level?

     While I totally agree with the authors “myocardial infarction should be included in the differential diagnosis of chest pain in sickle-cell disease despite normal coronary angiography”3 I want information that can help prevent myocardial infarction in my patients. Circumstances are crucial in the welfare of sickle-cell disease patients.4 What, then, were the circumstances of this particular episode? What was this lady’s alcohol intake like? A 44-year-old Hb SC man I once described (Case history 85, page 503)2 “drank Campari and brandy continuously for about 8 hours having had little to eat before going to bed. At 4 am the next morning (12.6.67) he was woken up with severe retrosternal pain ..”2. Cardiologist Professor Silas Dodu not only confirmed myocardial infarction (ECG’s on pages 504 to 508 of my book)2 but also made the correct phenotype diagnosis of Hb SC disease even before electrophoresis report arrived.2 Warned off alcohol, he abstained for 12 months but “the patient died at home after a history of drinking spirits”.2 Alcohol effect on the heart and lungs has been described in sickle-cell states5 so we need to know more about this lady.

Incidentally, insisting on raising transfusion levels of sickle cell disease patients to 110 g/dL (ie 11 grams per deciitre) as sometimes happens in the UK, continental Europe, and the USA can cause what I have come to call “hyperviscosity encephalopathy” which manifests itself with severe headaches, disorietaition, fits, and sometimes such mental symptoms as make doctors call in a psychiatrist. Not necessary. Just quickly remove a substantial amount of the transfused blood, to get the haemoglobin down to between 8 grams and 9 grams per decilitre. Watch the patient, more than you watch the patient’s blood.               

I declare that I have no conflict of interest except that I have a book ‘The Sickle Cell Disease Patient’ (Home Page) and I had 2 brothers and 1 sister with Sickle Cell Disease. My conflict of interest lies in the fact that any time I read about patients given Heroin or Morphine, or over-transfused, and causing complications, I assume them to be my own brothers and sisters. 

Felix I D Konotey-Ahulu

felix@konotey-ahulu.com

Kwegyir Aggrey Distinguished Professor of Human Genetics, Faculty of Science, University of Cape Coast, Ghana, and Consultant Physician & Haemoglobinopathy Genetic Counsellor, 10 Harley Street, London W1N 1AA, England

1    Ringelhann B, Konotey-Ahulu FID. Haemoglobinopathies and thalassaemias in  

     Mediterranean areas and in West Africa: historical and other perspectives 1910–1997 A

     Century Review. Atti  del’Accademia  della Science di Ferrara 1996; 74: 267-307.

2   Konotey-Ahulu FID. The sickle cell disease patient: natural history from a clinico-

     epidemiological study of the first 1550 patients of Korle Bu Hospital Sickle Cell Clinic. Watford:  

     Tetteh-A’Domeno, 1996.

3    Pavlü J, Ahmed RE, O’Regan DP, Patridge J, LefroyDC, Layton DM. Myocardial infarction in  

       sickle-cell disease. Lancet 2007; 369: 246.

4    Konotey-Ahulu FID. Sickle-cell disease and the patient. Lancet 2005; 365: 382-83.

5    Rubler S, Fleischer RA. Sudden death due to pulmonary thrombosis and infarction. Am J

      Cardiol  1967; 19: 867-73.           

Request from Geneva for patient in hospital in Colorado USA

In early June (2007) I got a frantic phone call from a lady in Geneva saying her brother “SC” was in hospital in Colorado with Sickle Cell Crisis, and had been on Morphine for 3 days, not getting better. Could I ring and advise? The patient, a professional pianist, was glad to talk to me. Within minutes, I discovered 5 precipitating causes of his crisis:

(1) Alcohol prior to illness
(2) Criss-crossing America flying
(3) Lack of sleep for 2 days
(4) Working too hard without a hoiliday
(5) Dehydration from not drinking enough water [He needed at least 2 Litres water daily]

I asked to speak to the Doctor and I told him (politely):
(1) Take him off the Morphine AT ONCE
(2) Hydrate him with 3 Litres of Normal Saline over 24 hours
(3) Injection Ketorolac subcutaneously 30 milligrams six hourly for just 3 times
(4) Get him out of bed as soon a possible
(5) Treat respiratory infection (if any).
(6) Oxygen to counteract the chest syndrome produced by the Morphine.

“And he will be out of hospital in 48 hours”. He was out of hospital in 48 hours. Alive.

Prof F Konotey-Ahulu.

Award Lecture in Philadelphia – May 5th 2007

PHILADELPHIASaturday May 5 2007         

AfricanAmericanMuseum In Philadelphia Award Lecture

Dr Felix I D Konotey-Ahulu is Kwegyir Aggrey Distinguished Professor of Human Genetics at the University of Cape Coast, Ghana and Consultant Physician in London. He delivered an unusual lecture at the AAMP Awards Ceremony in Philadelphia, USA, on Saturday May 5. He was one of 4 honorees including Naa Deedei Omaadru III of the Gã State and two African Americans, Nana Korantema Ayeboafo and Rev Dr Alyn E Waller.  Dr Konotey-Ahulu’s HUMANITARIAN AWARD Plaque was inscribed: “presented in recognition of your distinguished service and exceptional contributions to the people of Africa and to the world”. In response to this, and after thanking the AfricanAmericanMuseum in Philadelphia, Dr Konotey-Ahulu said his Award Lecture was in appreciation of the honor done him. The title of Dr Konotey-Ahulu’s Award Lecture was “The Remarkable African Ear: Phenomenon of Mid Pitch Arrest in Krobo/Dangme-Gã Tonal Languages of South East Ghana.” He described certain novel facts that are bound to surprise the leading Institutes of Linguistics worldwide. His abridged Power Point Lecture presentation appears below. The full Lecture will be placed in the Archives of the AfricanAmericanMuseum In Philadelphia. 

THE REMARKABLE AFRICAN EAR: Phenomenon of Mid Pitch Arrest in Krobo/Dangme-Gã Tonal Languages of South East Ghana

Dr Felix I D Konotey-Ahulu

ONE HUNDRED NAMES

What have the following in common? 1 Cannonball Adderley 2 Marian Anderson 3 India Arie 4 Louis Armstrong 5 Count Basie 6 George Benson 7 Brook Benton 8 Church Berry 9 Beyoncé 10 Clifford Brown 11 James Brown 12 Ray Charles 13 Nat King Cole 14 Natalie Cole 15 Ornette Coleman 16 John Coltrane 17 Sam Cooke 18 Miles Davis 19 Fats Domino 20 Billy Eckstine 21 Duke Ellington 22 Fantasia 23 Art Farmer 24 Ella Fitzgerald 25  Roberta Flack 26 Aretha Franklin 27 Marvin Gaye 28 Dizzy Gillespie 29 Dexter Gordon 30 Al Green 31 Lionel Hampton 32 Herbie Hancock 33 Donny Hathaway 34 Coleman Hawkins 35 Isaac Hayes 36 Jimi Hendrix 37 Lauryn Hill 38 Billie Holiday 39 Jonny Hodges 40 John Lee Hooker 41 Lightnin’ Hopkins, 42 Lena Horne 43 Whitney Houston 44 Freddie Hubbard 45 Jennifer Hudson 46 Mahalia Jackson 47 Michael Jackson 48 Milt Jackson 49 Ahmad Jamal  50 Al Jarreau 51 Alicia Keyes 52 Chaka Khan 53 B B King 54 Rahsaan Roland Kirk 55 Ertha Kitt 56 Gladys Knight 57 Patti LaBelle 58 John Legend 59 Abbey Lincoln 60 Jackie McLean 61 Carmen McRae 62 Wynton Marsalis 63 Johnny Mathis 64 Chares Mingus 65 Thelonius Monk 66 Lee Morgan 67 Charlie Parker 68 Oscar Peterson 69 Wilson Pickett 70 Bud Powell 71 Leontyne Price 72 Prince 73 Lou Rawls 74 Otis Redding 75 Lionel Ritchie 76 Max Roach 77 Paul Robeson 78 Diana Ross 79 Pharaoh Sanders 80 Jill Scott 81 Jimmie Scott 82 Archie Shepp 83 Bessie Smith 84 Sonnie Stitt 85 Art Tatum 86 McCoy Tyner 87 Usher 88 Luther Vandross 89 Sarah Vaughan 90 Dionne Warwick 91 Dinah Washington 92 Muddy Waters 93 Ben Webster 94 Randy Weston 95 Barry White 96 Joe Williams 97 Nancy Wilson 98 Jimmy Witherspoon 99 Stevie Wonder 100 Lester Young.  I repeat the question: So what do these people have in common?  ANSWER: They all have at least 3 things in common beginning with the letters A, G, and M which I interpret as ‘AFRICA’, ‘GENIUS’, and ‘MUSIC’.

Brawn plus Brain and Enforced Migration: When, through Enforced Migration, Slave Traders shipped Africans across the Atlantic they thought they were transporting just African brawn (muscle power) to work on the plantations. Little did the traders in human merchandise realize that they were also transporting African Brain. These one hundred highly talented African Americans (and there are many more not listed) are not only the tip of a huge brainberg but also the evidence (if evidence was required) that present day Africans have hidden treasures of brain-power that need to be brought out and placarded. One such hidden treasure is our Tonal Language in Mother Tongue. I shall prove this to you, using my own Mother Tongue, Krobo/Dangme-Gã.

Tonal Language: First of all, no Tonal Language should in this day and age be written without indication of how the word should be pronounced. I once mentioned this in a Lancet article in London (Saturday 29 April 2000 Volume 355, page 1559), pointing out that the word written ta has six meanings in Krobo/Dangme-Gã, and that mid pitch (the pitch immediately below high pitch in, say, CANADA) is exactly 3 semitones below high pitch. I want you to be part of this lecture by making you exercise your mental faculties. Pronounce CA NA DA at least 3 times – with the first ‘A’ high pitch, second ‘A’ mid pitch, and the third ‘A’ low pitch. You will find that the second ‘A’ is exactly 3 semitones below the first, and the third low pitch ‘A’ approximates to an octave below high pitch. Make high pitch ‘soh’ on the d r m f s l t d Tonic Solfa scale, and you will find that mid pitch is ‘m’ in tune, ALWAYS, whether you are a child, adult, male or female, British, Kenyan, American, or Australian. Just try it. Sing d r m f s l t d r m f s l t d Then, starting from a rather high level sing d t l s f m r d t l s f m r d and you will find that if you make the first s the pitch for Ca, then that for na is bound to be m. If you make d, your pitch for Ca then the mid pitch for na is l on the d r m Tonic Solfa scale. Without fail – exactly 3 semitones separating high and mid pitch, while the second s (the octave below upper s), or the second d (octave below upper d) approximates the pitch for da. Try the exercise again and again when you get home. I have said elsewhere that I consider Gã to be a ‘Major Key’ Tonal Language, while Krobo/Dangme is in ‘Minor Key’. It will not be difficult to identify which West African Tonal Languages are in ‘Major Key’, and which are spoken in ‘Minor Key’.

Tadka Equation Number One [3 Pitch Options]: I designed an equation some 7 years ago called ‘Tadka Equation 1’, which gave the number of reproducible sounds (and hence reproducible meanings) that a Krobo/Dangme-Gã word like ta or sentence like ta ta with two or more vowels (like ta ta ta ) will yield. S = pn x n where S is the total number of reproducible sounds, p the number of pitch options, and n the number of vowels. In other words, p to the power n, times n is equal to S. With ta n is 1 (just one ‘a’ in the word), p is 3 because there are 3 pitch options (high, mid, and low), so S (the number of ways ta can be pronounced reproducibly in the language) is 3 to the power one, times one, and the answer is 3 times 1, which equals 3 – ta (high pitch), ta (mid pitch), ta (low pitch). But suppose we see written ta ta, how does one pronounce this to make sense to a Krobo/Dangme-Gã native like myself?  Tadka Equation Number 1 will give S = p2 x 2 because there are two vowels in the sentence ta ta. Therefore 32 x 2 = 9 x 2 = 18. In other words, there would be 18 words with 9 different meanings. With ta ta ta S becomes 33 x 3 = 27 x 3, and there would be 81 vowel pronunciations with 27 different triple-word sentences depending on how each vowel is pitched. Do you understand what I am saying?   

Tadka Equation Number Two embodying 2 Quality Options: In my Lancet article referred to above ta has 6, not three meanings because in addition to 3 pitches there are 2 Quality options (q), namely the option of nasalizing the vowel, or not. So each pitch of the vowel can be pronounced nasalized, or not nasalized, and this conveys different meanings to words spelt the same way. Tadka Equation 2 is S = (p x q)n x n, that is p times q in brackets to the power n, times n. Therefore, for a one vowel word like ta the number of different and reproducible sounds equals (3 x 2)1 x 1 = 6. That was how I came to conclude in the Lancet that “the Krobo word written ta has six meanings (chew, war, giant-ant, fish out, narrate, palm tree) depending entirely on the tonal pronunciation”. As the number of vowels increase, so the number of different words that emerge becomes astronomical. To make the written words identifiable so that they approximate to the spoken word I decided to colour the sound. [Nasalization is indicated by a wriggle above the vowel. Ga (not nasalized) in Krobo/Dangme means ‘ring’, like wedding ring, but Gã (nasalized) is Accra, or Accra Language.

Colouring Sound: A New Linguistic Tool: High pitch I have coloured red, low pitch blue, and mid pitch is green. So the ‘a’ of Ca in Canada is red, that in na is green, and it is blue in da. CA NA DA. And remember that the pitch of na is exactly three semitones below that of Ca whichever key on the piano or organ you use as your high pitch. This is not only the first ever example of pitch variation quantification in African Languages but also the first time ever that sound has been coloured to facilitate learning of Tonal Languages. I have called it the Tadka Pitch Coloration (TPC) method of writing a Tonal Language.   

Remarkable African Ear and 4 Pitches: But the Krobo/Dangme-Gã tribal ear is able to discern that mid pitch can divide and give a lower mid pitch. The European may find it difficult to “quantify” this pitch but we tribesmen know that it is exactly 2 semitones below proper mid pitch. Any Gã person listening to me now will agree with this statement. Pronunciation of ‘Philadelphia’ where I am today affords the proof of this. Ponder the following reasoning.    

Philadelphia: Philadelphia has 4 syllables – Phi la del phia. One can pronounce Philadelphia any how and one will be understood. Whichever way it is pronounced the meaning does not change. Using the TPC method, the two most common ways of pronouncing the word are Phi la del phia (low-low-high-low pitches) and Phi la del phia (high-mid-lowermid-low pitches). Lowermid pitch is not some nebulous, vague, arbitrary, intermediate pitch as some Professors of Linguistics think. It is exactly 2 semitones below mid pitch. I have coloured it light green. If high pitch is s, and mid pitch is m, then lowermid pitch is r without fail on the drm Tonic Solfa scale. Exactly 2 semitones below midpitch! Therefore, thedel in the second pronunciation of Philadelphia sounds the note r in the ‘d r m’ scale. The brilliance of Tonic Solfa which is head and shoulders above piano or organ keys in music comprehension, is that while the same tune can be played in 12 different keys on the piano or organ, there is ONLY one way a hymn, or song, or ‘mother tongue’ can be sung or spoken in Tonic Solfa. You can play the Ghana National Anthem or British National Anthem in different keys (G Major, C Major, F Major, D Major, B Flat Major etc) but you can sing these anthems in only one Tonic Solfa medium. This is why the TPC (Tadka Pitch Coloration) method for Tonal Languages is a revolutionary concept. When Philadelphia is pronounced Phi la del phia the pitches are perfectly reproducible, and the differences in them quantifiable. Please repeat this statement over and over again until you understand it.

Achimota: Achimota is also the name of a town. It also has 4 syllables – A chi mo ta, but unlike Philadelphia Achimota should not be pronounced anyhow. Achimota presents an excellent example of the imperfect way our tonal languages have been written hitherto. The African native of the place is capable of pronouncing “Achimota” in ways that can convey meanings contrary to what is intended. Achimota is a sentence, not a word primarily. The way it is written makes people pronounce it A CHI MO TA(high-low-low-low), which means quite the opposite of what the native intended. This means: “One (someone) has been mentioned” (past participle) or, A CHI MO TA (low-low-low-low), which means “One (someone) was mentioned” (past tense; aorist). But neither of these was what the native Gã speaker intended. The correct sentence derived from fleeing slaves hiding in the bush near the road to Nsawam, warning others “Hush! Hush!! Name must not be mentioned, lest we are apprehended and sent back to the Slave Ship” – the correct sentence is A CHI I MO TA. [HIGH-MID-MID-LOW-LOW]. That is the correct sentence: A CHI I MO TA. Of the 5 separate vowels A i i o a in Achiimota only the first is not nasalized in the native rendering. The number of different renderings that a sentence with 5 vowels like this can (in theory) produce is given by the second Tadka Equation S = (p x q)n x n where the number of pitches is 3, number of quality options 2, and number of vowels is 5, so S = (3 x 2)5 x 5 = 6 x 6 x 6 x 6 x6 x 5 = 38,880. Thirty eight thousand eight hundred and eighty separate sounds that render 7,776 (seven thousand seven hundred and seventy-six) reproducible 5-word sentences of which just one (A chi i mo ta) is RECOGNISED as delivering the correct message. Herein lies the genius of the African ear.

The 3 Semitone Gap and Mid pitch Arrest: If the ability to pick correctly just one of 7,776 possibilities of pronouncing Achiimota with vowel pitch/quality variations is evidence of the African’s unique acoustic proclivities, the ability to isolate mid pitch, lock it in the brain, and produce it at will is even a greater mark of genius. It is like locking up in the brain the pitch of na as pronounced in Canada, and releasing it exclusively for certain words, and for those words only. The Krobo/Dangme words ta (war), bo (cloth), ho (honey), yo (hill), to (keep), le (know), ko (an or a), tɔ (bottle) bɔ(to age), ye (eat), so (conspire), Sɔ (Wednesday), zɔ (oil), ɔ, ε, a, (Krobo/Dangme words for ‘the’, depending on the ending of the accompanying noun), and the Gã word for ‘the’ (lε), are exclusively mid pitch and nothing else. Gã has very few words locked in mid pitch, but for Krobo/Dangme to have so many words pronounced only with mid pitch shows that these tribes have perfect mid pitch – a phenomenon that has not been known before to exist. One wonders how many of the 72 (at least) mother tongues in Ghana display this ‘mid pitch arrest’ phenomenon. It is as if the pitch between high and low pitches is suddenly arrested on its way down as one speaks, and reserved for certain nouns and verbs. Indeed, some Krobo/Dangme adjectives and adverbs do not escape this mid pitch exclusivity: tsu (tsutsuutsu) means red, (very red), gaga is tall, gagaaga very tall, and gbegbeegbe means ‘treacherously’. Pronouncing these words with other than mid pitch conveys other meanings to the hearers.   

One Human Race: English versus Krobo/Dangme-Gã: I shall test you. Pronounce “Proto-Agriculture”. Say it again. And again, slowly: Pro to a gri cul ture. How many pitches do you hear?I shall tell you.The Krobo/Dangme-Gã ear hears4 distinct pitches in the six syllables: Pro to a gri cul ture[low-low-high-mid-lowermid-low] – 4 distinct pitches with 3-semitone gap between high and mid pitch, then a two semitone gap between mid and lowermid pitches. Now, try humming what you have just said: hm hm hm hm hm hm and those of you who speak Gã will have just realized that you were humming the same pitches of “the frog’s fat”, translated into the Gã language kɔ kɔ de ne lε fɔ (low-low-high-mid-lowermid-low), the identical pitch sequence as in ‘proto-agriculture’. English sings the same Gã pitches without realizing it. To me, this is far more convincing evidence that there is but one human race, than that there are different human races. The difference between the African and the European is that these pitches mean everything to the African who must have them to communicate properly, while the European will get by with monotones when the same pitches are identifiable in the English language. To pronounce the last vowel with high pitch – kɔ kɔ de ne lε fɔ – would mean the frog brought forth! To make the former meaning more easily identifiable on the written page, I introduce an apostrophe (as in the frog’s fat), thus kɔ kɔ de ne lε’ fɔ.  Pitch-wise, the writing of my Mother Tongue has hitherto been placed in a European straight jacket, which I must discard to succeed in Adult Education in the tribe and be able to help the Ghanaian Krobo adult illiterate to read The Mother Tongue easily. I need to find new ways of communicating my message. The full unabridged lecture, describing vowel elongations with their variations in meaning, and other aspects of Tonal Languages including pronunciation of Ghanaian day names that African Americans and African Caribbeans may adopt if they wish – the entire lecture, with other aspects of Tonal Language like placing signs on vowels to help the colour blind in pitch recognition, introducing Tonal Braille for the completely blind, putting colour into Sign Language, and designing a Tadkafone for sound pitch and quality reproduction will be posted on the AAMP website.

The Way Forward: This exercise is aimed at making Ghanaians to want to read and write their Mother Tongue, and to teach it to others. We need to speak as many Native Languages as possible. To forbid the teaching of Mother Tongue in our Primary Schools is a tragedy. I repeat: To forbid the teaching of one’s Mother Tongue in our Primary Schools is a TRAGEDY. I myself speak Krobo/Dangme-Gã and Twi (Akrofi Twi of Akuapem) and I understand Asante Twi and Fante. I am not satisfied. I have made 2007 the year to learn Ewe (Anlo Ewe plus the minor variations of what is spoken at Hohoe and Peki). And I have a Konkomba Bible though I do not yet understand the language. The New Testament in the Konkomba language of Ghana is called Uwumbɔr Aagbapɔɔn Likpakpaln, containing 11 (eleven) vowels. The wrong ways of pronouncing this is counted in millions if there are both pitch and quality options. My Tadka Pitch Coloration method quickly identifies the exact and only correct native pronunciation. Meanwhile I am forever looking for the phenomenon of mid pitch arrest in African languages. By all means let us learn English, French, Portuguese and other foreign languages but, I repeat, to stop teaching our Mother Tongue in Primary School is a tragedy. Let every Ghanaian learn to speak at least one other Ghanaian language fluently. Let us preserve the pitch and quality of our spoken languages and teach them to our brothers and sisters in the Diaspora. Thank you for giving me the opportunity to share with you these priceless African treasures, aspects of which I see the African American and African Caribbean manifesting in all kinds of different ways. Thank you.  

GRATITUDE: I thank ALMIGHTY GOD for good health. I also thank (a) The African American Museum In Philadelphia Team (Dr Samuel Quartey, Dr Joy Riebow, President & CEO Romona Riscoe Benson and their Colleagues) for the  Award, which enabled me to give this Lecture on ‘The Remarkable African Ear’ (b) The Busby Sisters, Eileen Busby Keita and Margaret Busby OBE, for providing me with the names of 100 African American Musical Geniuses (c) Dr Benjamin Dodoo (not Dodoo) for his constant encouragement of me across the Atlantic (d) My beloved Rosemary (Ami-tor) Konotey-Ahulu for constantly being there for me these past 45 years of marriage (e) All of you on behalf of all the Award winners for coming to this Award Ceremony. The  name Tadka stands for Tεttεh-A’Domεno Konotey-Ahulu, the name I was given at birth, which revives the memory of my dear parents Rev & Mrs D A Konotey-Ahulu who taught me to sing any tune in Tonic Solfa, and much, much else.