Of a more general nature regarding health risk from food components is M.R.A.Morgan
& G.R.Fenwick (1990) "Natural foodborne toxicants", Lancet
336 (1990), 1492-5. They mention not only plant toxicants but also those from fish
and mycotoxins. A letter in Biotechnology
9 (1991), 198 supports caution in the use of Bacillus thuringiensis endotoxins as
insecticidal proteins in food plants, in response to an earlier article (see EEIN
1:5). Research into the binding of the insecticidal proteins to mammalian gut cells
is suggested, as part of the risk assessment.
Two summaries of the food safety legislation in the USA and the UK are in Lancet 336 (1990), 1557-62. In the USA the modified enzyme chymosin that is used to "set" cheese has been approved by the FDA: NS (3 Nov 1990), 12-3. There was a new food safety act in effect from the beginning of 1991 in Britain which allows the drawing up of regulations to require approval from the Ministry of Agriculture, Food and Fisheries for novel and genetically modified food: NS (8 Dec 1990), 5. The problems of the biotechnology industry in obtaining food or drug safety approval is a topic in Nature 349 (1991), 5. It points out that 1990 was not a good year in terms of the safety or registration of products.
For comments on the safety of eating food containing or made from GMOs see M.Geisow (1991) "The proof of the cloning is in the eating" TIBTECH 9: 5-7. It discusses some of the public concern over such foods. There is still a lack of unified European regulations on the use of food irradiation (Nature 349 (1991), 273, and it will be difficult to predict if unity will be reached in the regulation of the food safety of products containing GMOs.
One view of the politics of the product regulatory process in the USA is discussed in a new book by Sheila Jasanoff, The Fifth Branch: Science Advisers as Policymakers (Harvard University Press 1990), 302pp., which is reviewed in Nature 349 (1991), 116. She calls the fifth branch the advisory committees that serve the government regulatory committeees in deciding on the safety of varous substances. A letter from members of the FDA regarding the policy on approval of recombinant DNA proteins and drugs is in Biotechnology 9: 197-8.
A general mention of genetic technology was made in Newsweek (9 Jan 1991), 34-5, highlighting some of the expected advances in genetics, particularly their medical applications. Another comment on the business prospects of selling recombinant DNA produced human growth factors is in Scientific American (Feb 1991), 126-7. It lists some of the growth factors that are being tested. The use of recombinant DNA synthesised proteins in medicine will expand. Currently in the USA ten drugs made using these techniques have been approved by the FDA, but 104 await approval, and it is estimated that by the year 2,000 50% of all drugs approved could be made using recombinant DNA:JAMA 265 (1991), 16-7. An editorial in Biotechnology 9 (Feb 1991), 101 suggests that 1991 promises much in the way of new licensed products.
In reply to a paper describing some side-effects in children being treated with human growth hormone (see EEIN 1: 6), there are a series of letters on the safety of growth hormone in Lancet 337 (1991), 108-110. They are divided in their criticism and support for the earlier paper.
The results of an international trial of 107 patients with hemophilia using recombinant factor VIII has found it to be safe and as efficient as the plasma derived product: R.S.Schwartz et al (1990) "Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A", NEJM 323: 1800-1805.
The safety of new recombinant proteins may be established, but it may be another question whether all patients who should get them can. This is the subject of R.Gabriel (1991) "Picking up the tab for erythropoietin", BMJ 302: 249-250. Many kidney patients in Britain do not receive this protein because of funding technicalities, i.e. whether it is prescribed from GPs or from more limited renal unit budgets.
The saga of bovine somatotropin (BST) continues with a paper on the European situation
by T.B. Mepham (1991) "Bovine somatotrophin and human health", BMJ
302: 483-4, calling for more independent and extensive trials. However, the Committee
for Veterinary Medicinal Products in Brussels has given a positive recommendation
to the use of BST in Europe; Biotechnology
9 (1991), 212; NS
(6 April 1991), 8. The product in question was Monsanto's "Somatech". The European
moratorium remains in effect until 31st December 1991. In addition to the US states
mentioned previously, several Canadian provinces, and Norway, Sweden, Denmark, and
the Netherlands have so far banned the use of BST. Additional papers not previously
cited include S.S.Epstein (1990) "Potential public health hazards of biosynthetic
milk hormones", International J. Health Services
20: 73-84, 573-82. These papers are critical of the decisions that BST is safe for
human use, and of the business reasons that favour its approval in the USA, including
attacks on the FDA approval system. It includes mention of the database on BST,
which has only allowed input from particular scientists, excluding independents who had
more negative reports on BST.
There has been much response to the series of articles by Ames et al (EEIN 1: 4, 20) on the carcinogen testing using rodents. Ames and Gold argued that synthetic chemicals pose little cancer risk to humans. The majority of DNA damage occurs as a consequence of oxidants produced during normal metabolism. A paper attacking the use of chemical additives in cows is S.S.Epstein (1990) "The chemical jungle: today's beef industry", International J. Health Sciences 20: 277-80. A paper arguing for the need for rodent carcinogen testing is by P.F.Infante (1991) "Prevention versus chemophobia: a defence of rodent carcinogenicity tests", Lancet 337: 538-40. It is written by a US Government official and discusses the methods used for assigning cancer risk.
Several new products were approved in the USA, including GM-CSF, G-CSF (in Europe also), and Interferon A to treat hepatitis C; Biotechnology 9 (1991), 316. It appears that even after the safety of recombinant DNA produced proteins and their efficacy have been shown, there is still the problem of funding for their use. Letters relating to the use of erythropoetin in the U.K. are in BMJ 302 (1991), 407-8. Studies have also shown that erythropoietin may have potential as a performance-enhancing agent for atheletes, therefore its supply needs regulation to prevent abuse; NEJM 324: 698. A cost breakdown of clinical use and a survey has been conducted, which is reviewed in comments in BMJ 302 (1991), 434-5, 592. An extensive collection on papers on the use of erythropoietin is in the proceedings of a workshop on the treatment of anemia with it, published as Erythropoietin in Renal and Non-Renal Anemias, eds. H.J.Gurland et al., Contributions to Nephrology Vol. 88 (Basel: Karger 1991). Another protein that is being denied because of cost is IL-2; BMJ 302 (1991), 372, 592-3. The results of an international study with another recombinant DNA based protein have been positive; The International Chronic Granulomatous Disease Cooperative Study Group (1991) "A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease", NEJM 324: 509-16.
The results of pathological examinations of the people who suffered from Eosinophilia-Myalgia that was associated with the use of tryptophan made from a genetically modified bacteria are presented in the journal Human Pathology 22 (1991), 1-21, in several papers. It also provides references of the other studies so far published. The actual studies into what contaminates caused the disease are still progressing.
The market for the sale of tissue plasminogen activator (TPA) is great, especially in countries that do not use streptokinase, like Japan. Despite the studies showing that the cheaper streptokinase is also safer Americans may still be using TPA; U.S.News & World Report (March 25, 1991), 69-70. Part of the reason for the continued use of TPA may be the large advertisement budgets of the companies marketing it compared to the money that can be spent promoting the low cost alternative. A paper on reducing the downstream processing costs in production of recombinant DNA proteins is in Biotechnology 9 (1991), 229-233. There may be regulatory hurdles to overcome using new methods.
The US FDA intends altering the rules for Orphan Drug Act, so that only if a new drug has significantly better efficacy can it be approved under the speedier orphan drug route; Biotechnology 9 (1991), 212. As discussed on p. 31, the US President's Committee on Competitiveness has recommended a low key regulatory approach to encourage biotechnology. A discussion on ways to close the abuse of this Act, while retaining the encouragment for the development of new drugs that it allows, is in J.G.Thoene (1991) "Curing the Orphan Drug Act", Science 251: 1158-9. Two papers on discussion of the biopharmaceutical regulations in the USA are in Biotechnology 9: 244-50, from the perspective of the industry.
Related to the question of GMO food safety, as opposed to drug safety, is E.L.Flamm (1991) "How FDA approved chymosin: a case history", Biotechnology 9: 349-51. It was the first food ingredient approved in the USA made via recombinant DNA technoogy. In Britain foods that are the products or involve the use of GMOs will need to be labelled as products of gene technology; Biotechnology 9 (1991), 227, 316. However, there is opposition to these guidelines by the UK Genetics Forum and Parents for Safe Food, who want more classes of foodstuffs that involve genetic engineering to be labelled. The European Commission Novel Foods directive is expected at the end of 1991.
The situation regarding medical waste which can often present hazards to public health is reviewed by C.C. Lee et al (1991) "Medical waste management", Environment Science & Technology 25: 360-3. The PCR can be used for identifying infectious diseases in contaminated foods; Applied & Environmental Microbiology 57 (1991), 707-11.
A new antiviral AIDS drug may soon be approved in the US by the FDA, which has placed it on the top priority track. The drug is dideoxyinosine, which has been developed by Bristol Myers, and has the trade name VIDEX; Science 252: 206-7. Trials involving 23,000 patients have shown that it leads to similar improvement as compared with AZT, but may have fewer side effects. The work on the design of drugs that attack the sensitive structures that are associated with the action of HIV is discussed in Science 252: 31. Comment on the discovery of AZT is in Science 251: 1554, a longer examination of the patent for AZT is in the AJLM XVII: 144-180. The NIH is also considering joining the law suits against Burroughs welcome (EEIN 1: 35), for a share in the annual profits of US$350 million from the sale of AZT.
GM-CSF, G-CSF (in Europe also), and Interferon A to treat hepatitis C; JAMA 265: 2315; Biotechnology 9: 316; Nation's Health (April 1991), 9. This type of nonA or nonB hepatitis infects about 150,000 in the USA each year, and so large quantities can be expected to be used. About one half of the trial patients showed improvement after 6 months, but others had side effects, so it is still not a cure. The use of interferon alpha-2a against Condylomata Acuminata (genital warts) was not found to be effective; JAMA 265: 2684-7.
A protein that is reportedly being denied because of cost is IL-2 (EEIN 1: 34), the case in question is discussed in BMJ 302:1041. On the cost of Factor VIII see a letter in NEJM 324: 1515-6. On a more positive note there are reviews on the use of erythropoietin in NEJM 324: 1339-44, 1360-2. On the general use of hematopoietic growth factors see BMJ 302: 1164-5. On the use of growth hormone in elderly people see Lancet 337: 1131-2.
One of the expensive products is TPA (EEIN 1: 34). A paper describing the results presented at a conference of a clinical trial involving 46,000 patients testing the use of the clot dissoling agents, TPA, streptokinase and antistreplase is in BMJ 302: 1259-61. The results suggest that streptokinase should be used, but as discussed the financial interests may continue to affect the preferences for these compounds. Although the effectiveness of all drugs is the same, the TPA appears to induce many more strokes than streptokinase, so a switch in American presrciption practice should OK, in addition the cost of TPA is ten times more!
On research into safer materials for long term implants into the human body see Science 252: 1059-60. There is the possibility of a large research budget being set aside for this research in the USA. A new type of filtration membrane for removal of viruses from protein solutions, an important risk factor, is reviewed in Nature 351: 420-1.
A comment on risk assessment in health care is in Nature 351: 176. The delays in the approval of new products by the FDA is discussed in Science 252: 201-3; BMJ 302: 1293. The trend is getting worse.
See Lancet 337: 904 for a German case over the licensing of loess soil as a medication. A study on German eating habits is discussed in Lancet 337: 1336. Drug availability is discussed in MJA 154: 233-4.
Continued comment on the use of carcinogen tests appears in Nature 350: 555-6, regarding reports in Mutation Research 257: 209-27, 229-306; see also Science 252: 902-4. They distinguish between the usefulness of tests for compounds that damage DNA, and the unsuitability of tests for compounds that do not damage DNA. The mechanism of carcinogenesis is also discussed. See also Lancet 337: 857-8, 973; MJA 154: 303-6.
The results of a study showing that another recombinant protein is clinically useful
are J. Nemunaitis et al., "Recombinant granulocyte-macrophage colony-stimulating
factor after autologous bone marrow transplantation for lymphoid cancer", NEJM
324: 1773-8. treatment reduced the risk of infection, and decreased the length of
hospital stay. A related letter is in BMJ
303: 123-4, and a general editorial on growth factors and chemotherapy is in Lancet
338: 217-8. The debate about the price of recombinant products continues, see J.E.
Sisk et al., "Recombinant erthropoietin and Medicare payment", JAMA
266: 247-52. A comment on the price of TPA versus streptokinase, and medicare payments
in the USA is in Biotechnology
On the safety of food from GMOs, especially on tomatoes with inserted Bt genes see letters in JAMA 266: 362-3, in response to an earlier article JAMA 265: 1429-36.
On the issue of enhancement of characters, or cosmetic medicine, a recent case of the misuse of human growth hormone was reported; New York Times ; Biotechnology 9: 593. An eleven year old child without growth hormone deficiency, who is a few inches above average height, is being given growth hormone by his parents. For six years he has had daily injections, at a cost of US$15,000, via the parent's insurance company. This is unethical, and such use should be prevented if there is to be confidence that the misuse of genetics will not be extended when gene therapy becomes efficient.
German research has found that a bacteriocin-producing Lactobacillus bacteria can prevent harmful bacteria such as Listeria monocytogenes from growing in German sausages. It is being suggested that the sausages be inoculated with small levels of the safe bacteria to prevent the growth of any harmful bacteria, which cause food poisoning; Biotechnology 9:697. This may be a safer preservative than using the chemical sodium nitrate, which is already banned in most European countries at the necessary concentrations to kill bacteria.
The powers of the FDA may be increased in the USA, at least that is what is recommended by a recent report; Biotechnology 9: 539-40. The recent actions of the FDA have been stronger, and support is expressed in a comment in Lancet 337: 1533-4. European drug regulation is discussed in Lancet 337: 1571-2; 338: 257. Letters on the subject of gifts of industry to physicians appear in JAMA 266: 61-3.
The FDA is expected to toughen up the advertising and label regulations for sunscreen lotions soon; JAMA 265: 3217-20. There is widespread medical criticism of the sunscreen lotion labelling in light of the increasing incidence of melanoma; BMJ 302: 1036-7.
The FDA is on the way to approving the use of the new antiviral drug for use against HIV, dideoxy-inosine (DDI) (see EEIN 1: 48), Nature 352: 269, 464. Another new drug, DDC, which can be used with AZT, may also be approved, and already some black market sources are supplying the drug.
The recall of products made using L-tryptophan from Showa Denko K.K. has been extended to include all food products made using that batch of tryptophan; FDA Consumer 25 (June 1991), 38-9. There are still several cases of the disease eosinphilia which are unaccounted for. A follow-up survey of the eosinophilia-mylagia syndrome patients in the USA is reported in JAMA 266: 195-6.
The safety of human insulin has been debated several times, in respect to the patient's
awareness of hypoglycaemia. See A.W. Patrick et al., "Human insulin and awareness
of acute hypoglycaemic symptoms in insulin-dependent diabetes", Lancet
338: 528-32. This study found no difference in the awareness of hypoglycaemia when
using porcine or human insulin (an increasing number of diabetic patients have died
of this in recent years). However, two other studies on larger samples found the
opposite results; BMJ
303: 617-22; M. Egger et al., "Influence of human insulin on symptoms and awareness
of hypoglycaemia: a randomised double blind crossover experiment", BMJ
303: 622-6. There seems to be a need for a large study of this question. See also
338: 950-1. See comments on a legal suit in Britain on this issue in BMJ
303: 601; Science
252: 1090. Also on diabetes see BMJ
303: 260-1; SA
(Nov 1991), 93-4;MJA
155: 211-2; on self-testing for diabetes see BMJ
303: 696-8; on insulin resistance see NEJM
325: 938-47; see also K.O. Dea, "Westernisation, insulin resistance and diabetes
in Australian aborigines", MJA
The case of the deaths from the consumption of L-tryptophan (see EEIN 1: 5) made in genetically modified bacteria is still being resolved, but it appears any L-tryptophan may be intrinsically dangerous: Nature 353: 490.
A review on interferons is S. Baron et al., "The interferons. Mechanisms of action and clinical applications", JAMA 266: 1375-83. On the use of recombinant blood clotting factor VIII see Lancet 338: 831-2. On the use of purified factor IX for treatment of hemophilia B see JAMA 266: 794. On the pharmokinetics of TPA see Clinical Pharmacology & Therapy 50: 267-7. On insulin-like growth factor see JAMA 266: 1937. On the use of growth hormone for children with chronic renal failure see Lancet 338: 585-90. On the use of GM-CSF see Lancet 338: 601-2. On the approval of new biotechnology products see BMJ 303: 599; Nature 353: 591; Science 253: 1353; Biotechnology 9: 947-9, also see a book review in NEJM 325: 896.
General comments on biotechnology and production of useful medical products are in TIPS 12: 317-9; Biotechnology 9: 1063-4; BMJ 303: 1282-3; TIBTECH 9: 337-8. There is still a lack of information for physicians.
On erythropoietin (EPO) to treat anemia or sickle cell disease see NEJM 325: 1175-6, and on the costs of it see NEJM 325: 1176-8; JAMA 266: 2705-6; also on expensive products (a monoclonal antibody, Centoxin) see BMJ 303: 1476-8. On the abuse of proteins see B.J. Spalding, "Black market biotechnology: athletes abuse EPO and HGH", Biotechnology 9: 1050-3. This concern was expressed earlier, but there are signs that it is already underway, and it may not be able to be easily detected. EPO increases the number of red blood cells, so can increase performance in the same way that training at high altitude can, but maybe by a greater degree.
On the safety of human insulin see letters in BMJ 303:1265-8; Lancet 338: 1213-5. On the safety of alpha-interferon see Lancet 338: 1268-9, and on the safety of interleukin-2 see Lancet 338: 1464.
There is some preclinical data to suggest that recombinant IL-6 could be useful in relieving the side effects of cancer therapy; GEN (Nov/Dec 1991), 15. On the use of tumour necrosis factor (TNF) for therapy see A.G. Porter, "The prospects for therapy with tumor necrosis factors and their antagonists", TIBTECH 9: 158-2. On the use of gamma interferon for chronic granulomatous disease see NEJM 325: 1516-7.
On hemophilia A see R.J. Kaufman, "Developing rDNA products for treatment of hemophilia A", TIBTECH 9: 353-9. It especially discusses blood clotting factor VIII. On artificial blood see BMJ 303: 1348-50.
On aerosol delivery systems for therapeutic peptides and proteins see GEN (Nov/Dec 1991), 1, 51. There is research on the delivery of insulin, lung disease proteins such as cystic fibrosis. The advantage is that it avoids contact with the digestive system enzymes, and does require injection (which requires parental attention for children). It may also be used for gene therapy (EEIN 1: 81). On peptide targeting see TIBTECH 9: 295-7. On an electrically erodible polymer gel for drug release see Nature 354: 291-3. On drug delivery through the skin see SA (Nov 1991), 93-4.
The FDA has given its verdict on the L-tryptophan and eosinophilia-myalia syndrome (SG 175). The disease was caused by a toxic compound EBT formed when acetaldehyde reacted with L-tryptophan, and it could have been removed by a simple charcoal filter; NS (23 Nov 1991), 16. In future, the FDA will regulate the sales of L-tryptophan as a drug, requiring more testing (several years).
On the FDA rules for genetically modified food and drugs see Biotechnology 9: 1039, 1313; Nature 354: 173; Science 254: 1113; Lancet 338: 1449; JAMA 266: 2950. There may be a US$200 million annual sales cap on drugs allowed under the Orphan drug regulations (which are to speed up approval for new drugs), SCRIP Notes (11 Dec 1991), 15. See also American Pharmacy 31: 874-7; MJA 155: 421.
On European drug regulations, and who will decided in the future single EC in 1993 see Lancet 338: 1113-4.
A recent report on assessing the safety of foods produced using GMOs is Strategies for assessing the safety of foods produced by biotechnology, A report of a joint FAO/WHO Consultation Group (Geneva: WHO 1991). It is 58pp. but includes a useful summary of the issues involved. Like some other reports (SG 168-70), it recommends that special regulations should not be required unless novel substances are introduced to foods by genetic engineering. Many genetically engineered varieties will not contain novel substances, rather the levels of proteins that are already consumed may be altered so that only checks on the safety of these components are required to ensure safety.
The L-tryptophan and eosinophilia-myalia syndrome appears to be settled (EEIN 2: 6) in terms of the cause, see also Lancet 338 (1991), 1512; Biotechnology 10: 5; JAMA 267: 77-82. On the high resolution removal of viruses from protein solutions using a novel membrane structure see Biotechnology 10: 182-8.
Some new rumours have emerged about the safety of bovine somatotropin (BST). There are suggestions that data has been hidden which shows a link between BST and birth defects in cattle that were given it; NS (18 Jan 1991), 13. The European Commission is further delaying the decision whether to approve the use of it until there is further data made available on this, or further studies done. A comment by H.I. Miller the director of the Office of Biotechnology of the FDA that attempts to end the BST controversy is in Biotechnology 10: 147, claiming that all the data shows that BST is safe. It appears that the controversy will continue! Also see Lancet 338 (1991), 1513. A discussion of the issue in Europe is in Biotechnology 10: 148-9.
The molecular structure of human growth hormone and its receptor is described in Science 255: 306-12. On the possible misuse of growth hormone to make children grow taller see BMJ 304: 131-2.
An FDA panel (the blood products advisory committee) has approved two versions of blood clotting factor VIII; Biotechnology 10: 15. One was developed by Genentech and is sponsored by Miles, and another was developed by Genetics Institute and sponsored by Baxter International. Patients with hemophilia A can expect to be using these.
A review on the use of IL-2 for immunotherapy, including the last 5 years experience as a cancer therapy; Biotechnology 10: 157-62. The data suggest that IL-2 is effective in stimulating cell-mediated immunity without systemic toxicity. The FDA has been recommended to approve the use of IL-2 for treatment of patients with terminal kidney cancer; Nature 355: 287. Cetus has spent over US$100 million on the development of IL-2, called Proleukin, so they may be rewarded. A letter on problems of interferons is in JAMA 267: 508-9.
The FDA is also approving the use of diptheria and tetanus toxoids and acellular pertusis vaccine; JAMA 267: 485.
The possibility of using chemically synthesised oligonucleotides as drugs is discussed in Nature 354: 505. On the use of mixed micelles in drug delivery see Nature 355: 279-80. On using monoclonal antibodies to treat sepsis and septis shock see BMJ 304: 132-3. A review is J.M. Dwyer, "Manipulating the immune system with immune globulin", NEJM 326: 107-6.
Rules on the safety of food and foodstuffs made by organisms developed using recombinant DNA technology have been released by US, European; Biotechnology 10: 251; Science 255: 1631, and Japanese governments. The Japanese Ministry of Health and Welfare published a bilingual explanatory book on the guidelines to be used. A committee can determine whether a product is novel, in which case it must undergo much toxicity testing, or whether it is not (see a review of this in my new book, on back page).
Last year saw the introduction of another group of proteins produced by recombinant DNA technology. The 1991 US sales of colony stimulating factors , hormones that stimulate white blood cell production, were US$272 million. Three companies sold them. By 1996 the sales could be US$2 billion; Biotechnology 10: 362. Immunoconjugate products, based on monoclonal antibodies may soon be approved for wider use; Biotechnology 10: 246. The protein IL-2 is expected to be soon approved for treating renal cell carcinoma, following positive recommendations from the FDA advisory committee that investigated it; Science 255: 528; Biotechnology 10: 244; JAMA 267: 1716,9.
A commentary on the problems of using human insulin to treat diabetes is in Nature 356: 375-6. In the UK alone, about 20,000 patients of the 250,000 diabetes could be involved in lawsuits involving the alleged side effects of human insulin. Human insulin was introduced despite a lack of evidence that it had much clinical advantage over the older product, porcine insulin.
A much more controversial case must be the use of tissue plasminogen activator ( TPA ) to avoid blood clots, over the much cheaper treatment with streptokinase used with aspirin, following the results of a major study; Third International Study of Infarct Survival (ISIS-3), "ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs antistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction", Lancet 339: 753-70, editorial p. 780-1.
More studies suggesting erythropoietin may be useful in the promotion of red blood cell production before operations are in Lancet 339: 773-5. The cost benefits of using erythropoietin to treat renal disease, in avoidance of anemia and the need for blood transfusions, are presented in BMJ 304: 474-7. Haemoglobin itself can be genetic engineered and such a product may be a suitable blood substitute ; D. Looker et al., "A human recombinant haemoglobin designed for use as a blood substitute", Nature 356: 258-260, Nature 355: 777. There are many hopes that a blood substitute may be developed; SA (Feb 1992), 87, and this may be it.
A method to clear lungs blocked by cystic fibrosis using aerosolized enzyme appears to improve lung functioning; R.C. Hubbard et al., "A preliminary study of aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis", NEJM 326: 812-5. On the use of oral delivery of proteins and packaging techniques see SA (Feb 1992), 84.
For more comments on the safety of BST see International J of Health Sciences 21: 561-4. The FDA has hired an additional fifty experts to aid the approval of biotechnology products; Biotechnology 10: 344. Comments on the appointment of David Kessler to the head of the FDA in the USA are in the Hastings Center Report (Jan/Feb 1992), 5; Nature 356: 279.
The FDA has released its long awaited report on judging the safety of food products made by genetic engineering, and it will exempt them from case by case review unless there are signs that there will be a problem, for example an allergic reaction. This has been criticised by some, especially the decision to leave it up to industry to decide, and also that labels may not be necessary for some products; NY Times (1 June 1992), A17. An FDA survey on food labelling in general is in FDA Consumer (June 1992), 10-13.
The debate over the use of BST in Europe continues, comment is in Chemistry & Industry (3 Feb 1992), 84. The major issue is whether social and ethical factors should be added to the decisions regarding acceptance of new products. The answer from a bioethical viewpoint and from other traditions in the law is that yes they should, there are restrictions on some laws, such as on patenting of subject matter that is offensive to public morality, or protection of public health or public morality in other areas. We should focus attention on who should decide what is ethical or not.
The procedures of approval of glycoproteins (usually made by recombinant DNA technology) worldwide and under the US Orphan Drug Act are reviewed in TIBTECH 10: 114-20. Comments on biotechnology product approval are in TIBTECH 10: 107-8; Biotechnology 10: 488, 490. Different schemes for cost analysis can indicate a savings or loss for the use of erythropoietin, S. Sheingold et al., "The impact of recombinant erythropoietin on medical care costs for hemodialysis patients in Canada", Social Science & Medicine 34: 983-991. The debate over which patients should be able to receive erythropoietin in the UK , and whether it should be restricted to only the offically designated conditions, is in Lancet 339: 878-9.
A short-term therapy for cystic fibrosis patients may be the use of DNase inhalations; M.L. Aitken et al., "Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A phase 1 study", JAMA 267: 1947-51. On the expanding roles of interferons see NEJM 326: 1491-3; 1456-63. Recombinant follicle stimulating hormone can be used to induce superovulation for infertility treatment; Lancet 339: 1170-1. Interleukin-2 has been approved by the FDA for treatment of kidney cancer; Lancet 339: 1224.
Recently the results of an international study on clot dissolving agents was completed, ISIS-3 (EEIN 2: 34); BMJ 304: 1454-5. Comment on the results, which indicated that the cheaper enzyme streptokinase was just as effectove as expensive recombinant tissue plasminogen activator (TPA) are in Lancet 339: 1225-7. A new use for TPA may be to restore blood flow to frostbitten limbs, which could save amputation; JAMA 267: 2008, 10. A review of the clinical success rates of recombinant versus conventional drugs is B. Bienz-Tadmor et al., "Biopharmaceuticals and conventional drugs: clinical success rates", Biotechnology 10: 521-5. Recombinant products have been more successful on those criteria, though it does not take into account the costs nor alternatives, which can be less favourable as shown in the case of TPA.
Criticism of the FDA policy of exempting most food products made from GMOs is in geneWATCH 8(2), 2. This is in contrast to the UK approach, which is to have independent review of all food products; Lancet 340: 300. It is certainly less worrying to have independent review of all food products, than to rely only on the 'expertise' of food companies. A list of risks from such food is in geneWATCH 8(2), 4-5. An article explaining the FDA policy is D.A. Kessler et al., "The safety of foods developed by biotechnology", Science 256: 1747-9, 1832; see also Biotechnology 10: 629, 717, 740-1, 742-3, 829, 830.
The other side of the case comes from the satisfied agricultural companies who expect to have genetically modified tomatoes, and other crops in food stores probably in 1993; GEN 12(11), 1, 21; 12(9), 3; Biotechnology 10: 748. Calgene's rot-resistant and flavour-enhanced tomato is expected to be first, followed by DNA Plant Technology "VegiSnax" carrots and peppers. The breeding may not mean costs are less, the Calgene tomato is expected to be twice the price of other tomatoes at its commercial launch. A paper looking at consumer attitudes to BST is H.M. Kaiser et al., "Consumer perceptions and attitudes towards bovine somatotropin", North Eastern J. Agricultural & Resource Economics (April 1992), 10-20.
The use of recombinant proteins for cancer therapy is discussed in BMJ 304: 1621-3; 305: 265-7. In the USA, many recombinant DNA products are in tests for drug safety with the FDA. A list with predicted time to approval is in GEN 12(11), 13. They also make the comment that the FDA examination time is expected to decrease following changes in FDA administration and policy. Comments on the European regulatory environment for medical products is in GEN 12(9), 9-10.
The relationship between US federal reimbursement systems and payment for (and use of) erythropoietin is discussed in GEN 12(3), 1, 10. The company Eli Lilly has said that it has a scheme in the US to allow access of all dwarf children to the growth hormone it produces, and will provide it to them if they have no insurance to pay for it; Biotechnology 10: 812. Meanwhile the NIH study on giving growth hormone to short children without a growth hormone deficiency is under review (see later sections); Lancet 340: 110. It is an orphan drug, also on the orphan drug debate see Biotechnology 10: 697. A review on Creutzfeldt-Jakob disease, which was associated with nonrecombinant growth hormone extractions, is P. Brown et al., "'Friendly fire' in medicine: hormones, homografts, and Creutzfeldt-Jakob disease", Lancet 340: 24-7.
The discussion over whether human insulin is associated with hypoglycaemia has intensified, with calls for major studies in BMJ 305: 324-5, 351-7;Lancet 340: 301-3 (EEIN 2: 34). The hope that a pill may eliminate the need for insulin are still in the future; NS (27 June 1992), 17. There is still research being conducted into the contaminant associated with L-tryptophan; Nature 358: 96 (EEIN 2: 6). A review is S.T. Crooke, "Therapeutic applications of oligonucleotides", Biotechnology 10: 882-6.
The FDA has established a faster review process for new drugs; Biotechnology 10: 624. Importantly international harmonisation of preclinical trials has been made, so that less duplicate testing will be done. Currently a company can spend on average 12 years and US$230 million developing a new drug; Biotechnology 10: 620-1. The FDA has a global role; FDA Consumer (July 1992), 14-7. A new product interleukin-2 made by Centocor failed to win approval in the USA; Biotechnology 10: 616-7. The bioavailability of IL-2 when reconstituted with albumin is reported in Lancet 340: 241.
The favourable industry and investor reaction to the FDA decision not to impose additional regulations on products made from GMOs is discussed in GEN (Aug 1992), 26-7. They discuss the Flavr Savr tomato of Calgene, and predict a good future for agricultural biotechnology. That tomato is expected to be on sale in March 1993, and they have approval for commercial growth. The FDA has said it intends maintaining the food policy with no extra regulations; Bio 10: 962. The policy and safety continues to be debated; Biotechnology 10: 958-9.
A committee to examine ethical issues related to genetically-modified foods has been set up in the UK; NS (10 Oct 1992), 11. It will be chaired by Rev. John Polkinghorne, Queen's College, Cambridge.
A call for food labels on biotechnology-derived products is made in the newsletter of the Texas A&M Center for Biotechnology Policy and Ethics, Sept. edition. There is data to suggest that Americans have positive attitudes to food products made by biotechnology, but they want to see labels on the food products. They also report that over 1500 restaurants in the USA have formed a coalition vowing not to serve genetically engineered food (as reported on the August 3rd program on National Public radio). Meanwhile some restaurants in the USA are putting up signs to say that they do not serve genetically engineered foods; Nature 359: 8. A call for truth in advertising food is made in Biotechnology 10: 1056.
Public opinion about food safety in the USA (Seattle) and Japan (Kobe) is compared in R.A. Jussaume & D.H. Judson, "Public perceptions about food safety in the United States and Japan", Rural Sociology 57: 235-49. They found higher concern in Kobe than in Seattle, and it is interesting to relate this information to the attitudes people have about consuming foodstuffs made from GMOs as described in Attitudes to Genetic Engineering. A US study on attitudes to beef eating is M. Zey & W.A. McIntosh, "Predicting intent to consume beef: normative versus attitudinal influences", Rural Sociology 57: 250-65.
A list of some research projects that are developing (or have already developed) new food varieties of plants are reviewed in SA (Sept 1992), 118-9. Research on improving potatoes for frying, by reducing the water content (which reduces the oil content of fried potatoes) is described in Science 257: 1480. Research on improving food quality and characters in Japan is in Bio 10: 952-3. Such research could pose problems for developing countries who export food, if they do not also adopt new food products.
Earlier in 1992 the Health Council of the Netherlands submitted a report on the testing procedures for foodstuffs and products made using biotechnology; Network (Aug 1992), 14. They include the use of decision-trees to help aid consideration of foodstuff testing requirements. In the Netherlands a white chrysanthenum made by genetic modification is being used as a test of the EC commercial growth regulations for GMOs; Nature 358: 614. In the USA, the Calgene tomato presents many more potential problems so is considered a better test case.
New reports on bovine somatotropin (BST) have called for more research on the secondary effects it may have on increased level of antibiotic residues in milk; Nature 358: 614; Lancet 340: 782 US General Accounting Office, Recombinant Bovine Growth Hormone: FDA Approval Should Be Withheld Until the Mastitis Issue is Resolved (GAO/PEMD 92-26, 6 Aug. 1992); (EEIN 2: 48, 62). The reason is that the use of BST increases inflammation of the udder, mastitis, which may require more use of antibiotics, with the danger of these being passed to us. It also considers whether the milk from the 700 cows in the experimental herds should be consumed.
The use of medicines, and recombinant DNA produced hormones to enhance sporting performance is becoming impossible to monitor as discussed in Bio 10: 1067.
Preliminary studies suggest that the use of recombinant DNA produced colony stimulating factors (CSFs) may increase the effectiveness of AZT in combating AIDS; GEN (15 Sept 1992), 1, 21. Large scale clinical studies are underway in the USA. Discussion of alpha 1-antitrypsin is in Lancet 340: 402-3. A letter on the use of deoxyribonuclease I in treating cystic fibrosis is in NEJM 327: 571 (original paper in NEJM 326: 812-5.
There have been some responses to the recent calls for studies to examine the link between recombinant insulin and hypoglycaemia (EEIN 2: 62), see Nature 359: 355; Lancet 340: 469-71. A letter on the possible litigation over the injuries suffered from the tryptophan poisoning is reported in BMJ 305: 647. The use of fine-pore membranes to remove viruses from biological drugs is discussed in SA (Sept 1992), 120-1.
The monitoring of the expensive recombinant product erythropoietin is reported in N.R. Powe et al., "Access to recombinant erythropoietin by Medicare-entitled dialysis patients in the first year after FDA approval", JAMA 268: 1434-40. The insurers provided coverage to most people who had a medical use of the product quickly, but further monitoring is called for.
The regulatory and safety testing delays in agricultural biotechnology products are discussed in GEN (1 Nov 1992), 12-3. It discusses market research and scaling up procedures, and field tests, all of which require time. Comments on the protest activities of Jeremy Rifkin, and the campaign against foods from GMOs is in Biotechnology 10: 1406-7; NS (14 Nov 1992), 13-4. See also Nature 360: 101; JAMA 268: 2620.
A symposium report on the use of human growth factors as new therapies for perinatal disorders is in GEN (15 Oct 1992), 1, 18. The use of cell molecules involved in signal transduction as new drugs is being pursued in several companies; SA (Nov 1992), 85-6. Some individual US hospitals are developing guidelines for the use of new biotechnology drugs, even before final FDA approval; GEN (15 Nov 1992), 1, 17.
An updated report on the contaminated L-tryptophan batch that resulted in 38 EMS deaths and 1511 total reports of EMS sickness is in JAMA 268: 1828. A letter on human insulin and awareness of hypoglycaemia (EEIN 2: 62, 76) is in BMJ 305: 957.
On the FDA genetically engineered food regulation policy a series of questions and answers are in FDA Consumer (Jan/Feb 1993), 10-14. Campbell Soup company in the USA has decided not to use Calgene's Flavr Savr tomato until it is publicly accepted; Biotechnology 11: 152-3. A report from the American Society of Hematology Annual meeting reviewing the successful trials of cytokines as agents to stimulate hematopoiesis after chemotherapy is in GEN (Jan 1993), 1, 3, 16. Two reviews of cytokines are F&S 58 (1992), 1093-9; Immunology Today 14: 18-24. A review of the role of IL-1 in disease is in NEJM 38: 106-13.
The approval of recombinant blood clotting factor VIII for use by hemophilia patients in the USA, will save them fear of contracting further blood-borne diseases; Science 259: 32. On clot-dissolving drugs, JAMA 268: 195-6.
In Japan, the use of b-interferon is covered under national health insurance for treatment of hepatitis C; Yomuiri Shinbun (16 Jan 1993), 1. It reportedly works for 40-50% of people, after one and a half year's treatment.
A report of eosinophilic fasciitis associated with L-tryptophan ingestion is in MJA 157 (1992), 329-30. The usefulness of activated charcoal to absorb poisons is still to be fully resolved; BMJ 306: 78-9. A fatal side effect, hepatic decompensation, has been reported in several patients using alfa interferon; BMJ 306: 107-8. Resistance to erythropoietin is discussed in NEJM 328: 73-80, 205-6. Data suggesting that human insulin per se does not affect the presentation of hypoglycaemia is in BMJ 306: 167-71.
An explanation of the FDA procedures for safety evaluation of foods made with new biotechnology is in JAMA 269: 910-2.
Human growth hormone from the US company Biotechnology General has received orphan drug status for treatment of wasting syndrome (cachexia) in AIDS patients; GEN (1 Mar), 30. A survey of US high school students found that 5% of the males were using growth hormone in hopes of enhanced sporting performance, and 0.5% of the women, in two mid-Western high schools; Clin. Pediatrics 31 (1992), 723-6. Adolescent users of anabolic steriods have been found to tend to use other drugs also; NEJM 328: 922-6. In the UK families of victims of Creutzfeld-Jacob disease, due to pituitary gland extracted growth hormone, are claiming damages like those given to AIDS victims of blood transfusions; BMJ 306: 607. Some power athletes in the former USSR continue to use cadaveric growth hormone, adding the risk of disease transmission; Lancet 341: 768-9. In the USA, a special NIH committee has decided that trials of the use of growth hormone in normal short children should continue; Science 259: 883.
There is still controversy over the use of bovine growth hormone ( BST ) in the USA. The winter edition of US National Boycott News featured articles on how to ensure a boycott against the products; Center for Biotech. Policy & Ethics Newsletter (1 Mar),3. In the UK, BST has been approved for marketing - but there is still an EC moratorium until at least the end of 1993.
The user fees of the FDA are discussed in Biotechnology 11: 276-7, 438-9. Safety trials of recombinant factor VIII for hemophilia treatment based on 95 children are in NEJM 328: 453-9. They recommend the use of the recombinant product. Letters on clinical use and symptoms of erythropoietin are in Lancet 341: 503-4; on interleukin-2 in Lancet 341: 628; and on interferon regulatory factors 1 & 2, Science 259: 971-4. A review of anticytokine therapies is JAMA 269: 1829-35.
The link between human insulin and hypoglycaemia is discussed in BMJ 306: 719-20; and the UK court case seems likely to be stopped due to insufficient evidence, BMJ 306: 814. Methods of treating hypoglycaemia are discussed in BMJ 306: 600-1; Lancet 341: 761. The self-monitorring of triglyceride concentrations has been associated with clinical advantages; BMJ 306: 493. The danger of hypoglycaemia due to accidental injection of insulin is reported in Lancet 341: 894.
A product update on recently approved recombinant products in the USA is in Biotechnology 11: 670. The US company Miles Inc. has received FDA approval to market recombinant factor VIII for treatment of hemophilia A; GEN (15 March 1993), 27. Chiron has received approval for beta- interferon (Betaseron) in treating multiple sclerosis ; Biotechnology 11: 538-9.
A further study looking at tissue plasminogen activator ( TPA ) to prevent heart attack moratility compared with the cheaper drug streptokinase has been released; GEN (1 Jun), 1, 35; Biotechnology 11: 651-2. The GUSTO study of 41,000 patients in 15 countries found that TPA and intravenous heaprin had about 14% lower mortaility over streptokinase and heparin. The biotech companies are happy with these new results, as previous studies (ISIS-3) had shown that TPA was not more effective and not worth the extra cost. The principal sponsor of this new study was Genentech, the company that sells TPA.
Many officials of companies have told the FDA that they oppose labelling of bovine somatotrophin ( BST )-treated cow's products; GEN (1 Jun), 3, 22; Science 260: 883; Nature 363: 107; Biotechnology 11: 656-7. They say it will make people fear BST unneccessarily. However, we could also argue for labelling based on socio-economic grounds, that consumers should be able to chose to buy milk from BST-treated or nontreated animals. The FDA has asked for public comments on labelling. Comments on how truthful labels are is in The Ram's Horn (May 1993), 1-3. The final report of a USA-EC document Methods of Communicating Biotechnology with the Public (Dec 1992, 20pp.) can be obtained from OAB, USDA, Room 1001, RPE, 14th & Independence Ave, S.W., Washington D.C. 20250-2200, USA). The considering how to label foods made from genetically modified organisms,Biotechnology 11: 656-7. Letters on the policy are in C&I (15 Feb 1993), 102; (1 Mar), 134.
On approval in the USA see Biotechnology 11: 554-5; Lancet 341: 1018-9. Meanwhile the EC Committee on Veterinary Medicinal Products has issued its final report saying that Monsanto's and Eli Lilly's BST are safe, though the moratorium continues until at least 31 Dec., 1993. On food insepction methods in general see SA (June 1993), 101-3.
The potential use of growth hormone as a therapy in adults is discussed in Lancet 341: 1247-8. Interferon's success in treating hepatitis C is discussed in a letter to BMJ 306: 1196. The use of erthropoietin ( EPO ) for 14 days before a hip operation decreases the need for blood transfusion; Lancet 341: 1227-32. Also on EPO see NEJM 328: 1498-9.
Research on the use of cytokines to treat osteoporosis is reviewed in Science 260: 626-7; and in cardiovascular disease see Biotechnology 11: 676-81. The use of IL-2 in immune response is reviewed in Science 260: 496-7. The use of fibroblast growth factor -1 to stimulate blood flow in tissue by improving blood vessels is reported in Nature 362: 844-6. Commercial research on the use of DNase treatment for cystic fibrosis is reviewed in Biotechnology 11: 580-2.
The revised FDA guidelines (Points to Consider) for monoclonal antibodies and cell lines are discussed in GEN (15 April 1993),1, 29. A trial of an antibody HA-1A to treat septic shock in dogs reveals further research is needed; JAMA 269: 2221-7. The successful delivery of insulin via aerosol is reported in JAMA 269: 2106-9.
The EC executive has proposed a 7 year ban on the use of bovine somatotrophin ( BST ) in Europe, ending several years of delays; Science 261: 418; Nature 364: 27, 565; Biotechnology 11: 869. The decision was not unexpected, and represents the introduction of socio-economic factors that may limit application of biotechnology. In the USA the American Medical Association is joining efforts to promote the acceptance of BST. However, there are now 8 BST-related bills in the US Congress, being considered by committees.
In Japan Shiseido is marketting rice without globulin as a health product, a new class of food, "physiologically functional food", which is an alternative for about 70% of the people who have allergies, Nature 364: 180.
Comments on how biotech products can obtain FDA approval is in GEN (15 June 1993), 6-7, 20. It suggests precontact with the FDA to know what is required, never cover adverse information (because it will always come out anyway). A review of medical uses of cytokines is in TIBTECH 11: 74-7. The use of recombinant DNase I to treat cystic fibrosis is reported in Lancet 342: 199-202.
Labelling of products produced from GMOs is a contentious issue. Why, in the age of increased information are many biotech companies trying to avoid labelling, a wise company should know that in a literate country such aversion to labels may turn into a negative public image. People have a right to information, and such information should be reliable and standardised. On the debate in Canada see The Ram's Horn , July, 1-3.
French scientists face court charges over the cases of human deaths due to Creutzfeldt-Jakob disease, following the death of a child treated with pituitary gland extracted human growth hormone, before the advent of the safe recombinant product; Science 261: 543; NS (31 July 1993), 4; BMJ 307: 281.
Chicago has passed a local law requiring all foodstuffs made from genetically engineered organisms to be labelled as such; Nature 365: 96. It is the first city to do so. Calgene plans to introduce its Flavr Savr tomato in shops in autumn with a label. A new perfume called "DNA perfume" claims not to contain DNA, Science 261: 826-7.
A review is J.F. Bach et al., "Safety and efficacy of therapeutic monoclonal antibodies in clinical therapy", Immunology Today 14: 421-5. It reviews a meeting from Dec. 1992. One of the most expensive therapies using an enzyme is that for Gaucher disease, reviewed in Lancet 342: 694-5.
An FDA advisory panel has approved Genentech's DNase as a treatment for cystic fibrosis, Biotechnology 11: 972-3; Lancet 307: 489. it is called Pulmozyme. Hypoglycemia in diabetes is discussed in NEJM 329: 876-7. A paper reporting results of factor VIII for hemophiliac use is in Lancet 342: 342: 700-3, 693-4. General comments are in Biotechnology 11: 1003-5; and product updates on licensing on p. 989, 1114.
The relationship of the human disease Creutzfeldt-Jakob disease to pituitary gonadotropins is discussed in BMJ 307: 517-8. In the UK two farmers have died of prion diseases that may be related to the bovine form (see section of Diseases & Vaccines above).
A summary of the regulatory processes for biotechnology drugs and products in the EC is in GEN (1 Sept 1993), 3, 36.