France is spending US$40 million in 1991, and US$50 million in 1992, on genome mapping
and sequencing: Human Genome News
2:5 (Jan 1991), 12. In France two private nonprofit groups (Centre d'Etude des Polymorphismes
Humain and Genethon) are spending more money than the French Government on genome
251 (1991), 623;BMJ
302 (1991), 120. Meanwhile in Japan the Ministry of Education, Science and Culture
has not provided much funding for genome research, and it is unlikely to provide
much over the next few years: Nature
349 (1991), 360. There are also some reductions in the expectations for US geneome
project funds: Science
251 (1991), 742-3.
The discovery of all the genes will result in a new way of thinking about what biology is, a shift from experimental biology to using computer-based databases. This is the theme of W.Gilbert (1991) "Towards a paradigm shift in biology", Nature 349: 99. Biologists have to adjust to use new methods for solving problems, including being hooked into computer databases, and using whatever testkits are available, and apply this to their biological problems.
Several US companies that have been set up to perform some of the research for the human genome project are mentioned in a report in Scientific American (Jan 1991), 86-7. The debate about how much is patentable from the project will continue, and depends to some extent on whether particular countries want private companies to perform such research or not.
A summary of the current US-funded model organism studies is in Human Genome News 2:5 (Jan 1991), 1-2. In includes description of the roundworm studies (C.elegans ), and projects in yeast, E.coli , Mycoplasma and mouse. A useful newsletter on the US DOE and NIH genome project is Human Genome News, which is distributed free of charge, apply to Betty K.Mansfield, HGMIS, Oak Ridge National Laboratory, P.O.Box 2008, Oak Ridge, TN 37831-6050, USA.
A paper by B.J.Thomas & R.Rothstein (1991) "Sex, maps, and imprinting", Cell 64: 1-3, discusses why the genetic maps found in males and females are different. When these maps are based on the frequency of crossing over the female maps are about 90% longer than the male maps! In physical length they are obviously not so different, and they propose a model to explain this based on the transcriptional activity of genes during the formation of gametes that occur as a result of imprinting. This would suggest that regions of the genetic linkage maps that have large gaps contain genes that are very active during gametogenesis. This will be able to be tested.
Letters regarding the human genome project in the USA continue, and several are in Science 251 (1991), 854-5; Nature 350 (1991), 104. They debate whether the objective of the project was really to sequence genes, or to look at genetic diseases in general, as an extension of existing projects with additional research funds. A summary of two recent meetings, including one of the NIH-DOE ethics committee is in Human Genome News 2 (March 1991), 9-10 & 15-16. Guidelines for human linkage maps based on the conclusions of a 1990 conference are in Annals Human Genetics 55 (1991), 1-6.
The genome sequences will provide a method to trace the history of molecular evolution in a detailed way, especially as fossil DNA remains can be sequenced and compared to current day sequences. A discussion on this was in Robert Pollack, "Genes and history", NS (8 Sept 1990), 44-5. His new book is entitled Reading DNA and is published by Harvard University Press, 1991. The sequences will not allow us to predict the future changes, and it will be dangerous for us to attempt to modify such sequences. The DNA sequence from 8,000 year old human tissue in Florida was recently reported; Nature 349 (1991), 785-7; Lancet 337 (1991), 608; NS (9 March 1991), 18. The sample used for PCR analysis was from brain tissue preserved in wet peat.
A comment on the rate at which genetic disease alleles are being mapped is by G.A. Nicholson (1991) "Mapping brain genes", Medical J. Australia 154:7-9. Many neurological diseases are being mapped, but there will be many more, and higher estimates suggest that 75% of our genes are expressed in the brain. Also of interest is a general paper supporting the genome project by Paul Berg (1991) "Reverse genetics: its origins and prospects", Biotechnology 9: 342-4.
A new DNA research institute is being built in one of the new science "cities" of Japan, in Chiba; Nature 349 (1991), 640. It will be funded initially by the local government and private sources, and is intended to be focused on developing DNA sequencing technoogy and the sequencing task. The funding of the genome project and genetic mapping in Europe is discussed in Nature 350 (1991), 261. A comment on the new U.K. funding is in Human Genome News 2 (March 1991), 1-3.
A review of the book Genes and Genomes, by Maxine Singer & Paul Berg (Blackwell/University Science Books 1990, pp. 929, 27.50) is in Nature 349 (1991), 752. It includes much of the history of genetics in eucaryotes, in addition to much biological explanation.
The proceedings of the XXIVth CIOMS Round Table Conference held in Tokyo and Inuyama
last Jul, have been publised as Genetics, Ethics and Human Values. Human Genome Mapping, Genetic Screening and Gene
eds. Z.Bankowski & A.M.Capron (Geneva: CIOMS 1991). The 200pp. document can be obtained
from CIOMS c/o WHO, Avenue Appia, 1211 Geneva 27, Switzerland. There are papers
on these three subthemes, covering the multidisciplinary conference. Two papers from
the Council for Responsible Genetics on genetic discrimination, and the genome project
appear in IJB
1 (Dec. 1990), 214-226.
A general introduction to the genome project is in J.Beckwith, "Foreword: The Human genome Initiative: genetics' lightening rod", AJLM XVII: 1-15. See the other references in the ethics section of genetic screening from the special AJLM XVII issue.
Genetic information has much potential to be used in schools and this is the subject of D.Nelkin & L.Tancredi, "Classify and control: genetic information in the schools", AJLM XVII: 51-73. The problem of classification of students on the basis of the results of the genetic screening is a key issue, and the privacy issues, misclassification of students in streamed classes, and the right to refuse testing. Recently I asked some Japanese students what they would do if they had a genetic or chemical method to improve the learning ability of their putative future children, would they let there children have more free time? Many responded that they would still want them to work hard, no mater what the improvements that could be made in easier ways. The question of education will be interesting in the future, as alternative methods to improve intelligence are sought. Most importantly there needs to be a decline in the desire for children to have high grades and high levels of memorised knowledge to be the judgement of a successful childhood.
A report on a project underway to prepare a map of the dog genome is in Science 252: 382; NS (8 June 1991), 18. Comments on research funding appear in Science 252: 490-3, 625; Nature 351: 11-2. Comments on the paradigm shift in biological research that the genome project results may bring, see Nature 351: 9.
The coordination of the European Genome research project is discussed in a new report, from the European Science Foundation, Report on Genome Research 1991 , reviewed in BMJ 302: 865. Discussion of European biological research organisations is in Nature 351: 91-2. On the subject of the US DOE's genome project see a report in Science 252: 498-501.
In EEIN 1: 41 a report on the use of fossil DNA was made. The oldest DNA so far isolated is from chloroplasts of a fossil magnolia leaf, at least 16 million years old. But their are biochemical doubts about DNAs survival over such a period; NS (11 May 1991), 44-48. The oldest living bacteria have been isolated from old Mastodon intestines, thought to be about 11,000 years old; NS (1 June 1991), 22; Quarterly Review (July 1991). The bacteria survived in a peat bog in Ohio for so long in the cold and anaeorbic conditions, in a state of suspended animation. The DNA of bacteria should have changed dramatically over such a long evolutionary period.
A book review of Joel Davis, Mapping the Code (294pp, US$22, Wiley 1991) is in Nature 351: 280. There will be increasing numbers of popular books about the genome project.
A special issue of the journal Bioethics
(July, Vol. 5, No. 3) is devoted to discussion of the human genome project and where
the map will lead us. It includes the following papers; D. Macer, "Whose genome
project?", p. 183-211; D.C. Wertz & J.C. Fletcher, "Privacy and disclosure in medical
genetics examined in an ethics of care", p. 212-32; L. Skene, "Mapping the human genome:
some thoughts for those who say "there should be a law on it", p. 233-49; B. Andreasaen
Rix, "Should ethical concerns regulate science? The European experience with the human genome project", p.250-256. These are all relevant to the ethics of the human
genome project, and cover the issues raised by it. The paper by Macer argues that
the information arising from the human genome project is common knowledge, and should
be shared by all of humanity. The owners are all people, and the control of the project
should not be left to those who fund the project, or the private interests that benefit
from the information. Wertz & Fletcher focus on the problems of disclosure of information obtained from genetic tests, and include reference to their international
survey of geneticists. Skene asks whether it is necessary to always create laws
to govern new developments, but rather we need only focus on the applications that
In the July issue of Human Genome News , p. 12-4, there three conference reports from U.S. meetings that considered the ethics of the genome project. The meetings were held in Houston, Washington D.C., and Minneapolis, and ask more questions about the genome project. see also P. Brown & D. Concar, "Where does the genome project go from here?", NS (17 Aug 1991), 13-4.
Favourable comment on the funding of the human genome project is in JAMA 265: 3132-4. On the question of huge scale science funding is the US space station project, which continues to be funded; Science 252: 1483. There is a debate going on as to the amount of extra money that should be spent to improve the accuracy of the genetic sequences that are determined, and computer programs to find some errors are available; Science 252: 1255-6. There is also debate on the extent to which a complete DNA sequence should be sequenced, and how human evolution should be traced; Nature 352: 567.
A paper on a new and cheap methodology for cDNA sequencing is M.D. Adams et al., "Complementary DNA sequencing: expressed sequence tags and human genome project", Science 252: 1651-6; see also Science 252: 1618-9;Nature 352: 20-1. They conducted automated partial DNA sequencing, and identified 337 new genes, and mapped many to chromosomes. It was done very quickly, and very economically, and is an alternative to the current genome mapping strategy.
The US HUGO office may be affiliated with John Hopkins University, so that it can receive US Federal funding; Nature 352: 3. There are also financial problems for the HUGO office in Osaka, Japan. A new HUGO office opened recently in Moscow, with Soviet Government funding; Nature 351: 683.
On the 11th gene mapping workshop see NS (17 Aug 1991), 5. After the workshop an extra 600 genes where reported mapped, bringing the total to about 2500. Baroness Warnock (23 Aug 1991) called for a Royal Commission in the UK to investigate the issues raised from the project.
On the question of data storage and publishing see M.J. Cinkosky et al., "Electronic data publishing and GenBank", Science 252: 1273-7. Their model is that the conclusions of sequence data are published in paper, but the data is in electronic databases. On the problems with the current US Genome Database see Nature 352: 94.
The Japanese Science and Technology Agency is setting up a new DNA analysis centre supported by private companies as part of the genome project in Japan; Nature 351: 593. The rice genome is also to be mapped, but the industrial collaboration will make problems for the immediate and free disclosure of information; Science 252; 1611. For comment on the progress of the genome sequencing of the worm, Caenorhabiditis elegans , see Science 252: 1619-20. The pig genome may also be sort; On the space station cutting off funds from other projects see Nature 352: 175. 352: 180.
Comments on big science funding appear in Nature 352: 272; Science 253: 128-30. On US federally funded research see Science 252: 1765. On the management of science see a book review in Nature 352: 390-1. A comment on the search for plant genes is in Plant Cell 3: 645-6. A new book is Joel Davis, Mapping the Code (294pp., 15, John Wiley 1991), reviewed in NS (10 Aug 1991), 47.
Future HUGO-organised Human Gene Mapping Workshop's may be reorganised because of
the large numbers attending; Nature
352: 747, 352: 117-8; Lancet
338: 502; BMJ
303: 487. In the 10th meeting in August the locations of an extra 600 genes, and
2000 additional sequences were announced. As of September, the grand total for mapped
genes was 2,316 and for sequences, 6,831. The estimated number of total genes in
humans may be 100,000; the number is increasing as sequencing of other genomes reveals
more genes than expected. In the year Sept. 1990 to August 1991, about 80 genes
for clinically recognised diseases were mapped. On a US meeting see Science
253: 376. HUGO will have a new director, Norton Zinder; Science
On research into the ethical issues see Lancet 338: 502; and an ASHG Human Genome Committee Report is in AJHG 49: 687-91. See also Nature 353: 2, 598; NS (31 Aug 1991), 8. On the usefulness of the sequence for research into human population genetics; Nature 352: 567; L. L. Cavalli-Sforva, "Genes, peoples and languages", SA (Nov 1991), 72-79. See also NS (28 Sept 1991), 56-7, (19 Oct 1991), 20; PNAS 88: 8720-4; Science 253: 1467, 1503-7. On sequencing ancient DNA see Science 253: 1354-6.
For a general review; E.D.Green & R.H. Waterston, "The human genome project. Prospects and implications for clinical medicine", JAMA 266: 1966-75. On scientific issues; PNAS 88: 7474-6, 7477-80; on the parameters of the human genome, and on radiation hybrid mapping, respectively. On new computer methods for sequencing; Science 253: 1489. As mentioned earlier, a single patent application for 337 human genes raises questions about the patenting policy; Nature 353: 485-6. However, there is no demonstrated utility, so in addition to ethical or policy issues, it may fail on this ground. There is a claim that many researchers are wasting much money in such patent applications for raw gene sequences; NS (7 Sept 1991), 22.
The Japanese government is spending more money on genome mapping, see Nature 353: 3; the new STA budget proposes spending US$11 million on genome research next year. Other agencies also finance such research, though the total is still relatively small. On international funding see Science 253: 255. On contracts from the NIH for genome research to private industry see Science 253: 743. The rice genome project is also being supported, by money from horse racing that is also financing a horse genome project; Nature 353:99.
The controversy associated with the patent applications for numerous human gene sequences
1: 81). The number of applications could rise greatly, as robotic machines could
sequence 75kbases of DNA a day, up to 100 genes. Critics of patenting claim that
it may discourage industrial investment; Science
254: 184-6, 1276; Biotechnology
9: 1310-11. There is still much doubt over whether the application will be successful;
354: 174. Nature
has called it the end of the innocence of new biology, though the data has little
value itself and it may be a miscalculation; Nature
354: 171-2; BMJ
303: 1286. The response from British genome sequencers at the MRC may be protection
of sequences; Science
254: 1583; BMJ
303: 1353-4; Nature
354: 96, 426, which would damage even further the ideal of data-sharing and the internationalisation
of the project, though it has been denied. The White House Office of Science and
Technology Policy is examining the issue of gene patenting; Science
254: 1104-5. The issue has very broad implications, and it would be useful to sort
it out as early as possible, at governmental levels.
A view from the biotechnology industry of the genome project is in B.F. Mackler & M. Barach, "The human genome project in the United States: a perspective on the commercial, ethical, legislative and health care issues", IJB 2: 149-57. There are not immediate commercial applications of the genome project, rather that will wait for diagnostic and therapeutic applications of the genetic knowledge. There are however, already some commercial spinoffs of the genome project, the techniques, information processing, sequencing machinery and other lab. machinery. On improved software for cell sorters see GEN (Nov/Dec 1991), 45. Improved computer programs for DNA data analysis are discussed in Science 254: 805.
A report on human gene mapping is in Nature 353: 798-9. The concerns about how well the databases of sequence reflect current progress are discussed in Science 254: 214-5, and the call is made for funding organisations to insist on sharing sequence data as a prerequisite for further funding support (or continuation of funding). Reviews of databases are in Science 254: 201-7, together with a pullout genome map of Drosophila, and a chromosome by chromosome account of the number of human genes mapped and the number of markers that have been reported. The remains of a 4,000 year old human in Austria are being utilised for DNA comparisons; Science 254: 187-8. There is increasing support for a genetic survey of all people's of the world; EEIN 1: 81; Science 254: 517.
A letter saying that the human genome project goal to sequence all the DNA is not beneficial as has been claimed is in Nature 353: 691; in contrast see FASEB J. 5: 2885; TIBS 16: 454-61. The NIH budget application breakdown is in Science 254: 791, for a total of about US$8 billion. The genome projects of other organisms are discussed in Science 254: 528, and on gene trees of mice strains see Science 254: 554-8. On the canine genome project see the New York Times (1 Dec 1991), C1, 12; and on Drosophila project see a review in Science 254: 221-5. On the evolution of genome size of birds; J. Heredity 82: 363-8.
A paper on ethics and the human genome is in BME (Oct 1991), 25-31. See also Science 254: 1664-5; Nature 354: 323. The role of HUGO as an intermediatory between many scientists is expanding; Science 254: 932. On the methodology of genome sequencing see Biotechnology 9: 1341-5.
Reviews of several recent books on the ethical implications of genetics, including a review of Shaping Genes, are in BME (Oct 1991), 32-3.
A controversy has arisen over the offer from an American millionaire industrialist,
Frederick Bourke, to set up a commercial company to complete the sequencing of the
C. elegans (nematode) genome, drawing two key scientists from other posts. Dr. J.
Sulston of the MRC Laboratory of Molecular Biology in Cambridge, U.K., and Dr. B. Waterton
from Washington University in St Louis, USA, have been cooperating on the sequencing
of the C. elegans
genome. There is a shortage of government money to complete the sequencing, so
the offer from the private company will allow the completion of the sequence, using
automated DNA sequencing technology developed by L. Hood in the USA. However, they
will want to attempt to patent the genes, though Sulston has said that he will only join
the project if the DNA sequence is immediately available to other scientists; NS
(1 Feb 1991), 13; (8 Feb 1991), 17; Nature
On the funding of the Genome Data Base at John Hopkins University, USA, see comments in Human Genome News (Nov 1991), 1-6. The contact address for the database is:
Michael A. Chipperfield; William H. Welch Medical Library; 1830 E. Monument Street, Third Floor; Baltimore, MD 21205.
On database contamination see Nature 355: 211.
The patenting of genetic material from the sequencing of DNA in the NIH case has been criticised by HUGO; NS (18 Jan 1991), 12. See also comments in Science 254 (1991) 1710-2; Biotechnology 10: 52,55; Nature 355: 103, 104, 194, 292. An NIH panel has criticised the decision to apply for gene patents; Biotechnology 10: 120. The future of HUGO and shared information is discussed in Nature 355: 4-5; see also Science 255: 27.
There have been some ownership debates over the remains of a person frozen for 4000 years, and these still continue, but now it appears that research will begin; NS (11 Jan 1991), 17-8; Lancet 339: 296-7. The corpse is in Innsbruck. Also on the genome project see a book review in JAMA 267: 299-300.
A paper on some of the ethical and practical issues of applying the results of human genome research is G. Geller & N.A. Holtzman, "Implications of the human genome initiative for the primary care physician", Bioethics 5: 318-325.
On the science of DNA sequencing see A.J. Kostichka et al., "High speed automated DNA sequencing in ultrathin slab gels", Biotechnology 10: 78-81. The output from the machine is about 450 bases of sequence information in less than one hour, though the instrument actually sequences 8000 bases of total DNA an hour.
A general editorial on the genome project is in JMG
29: 1-2. The debate on
genetic material was discussed above, in the patents section. The UK position is
that it is against patents, but the MRC also applied for patents in case patents
are awarded; BMJ
304: 725-6. Their case against patents would be stronger if they had not applied
for a patent. Rather after such an application for what they said would be unethical
subject matter for patents, we will only further doubt the ethics of the administrators and researchers involved with the UK genome effort. In any case, an early decision
on the validity of such patents is desired, and such a decision may come by June;
(21 March 1991), 12, following government pressure.
A discussion on the ELSI studies in the USA is in JAMA 267: 1715-6 (see also the conference reviews). A call for public involvement is made in JAMA 267: 653.
A review of the human genome project is in SA (April 1992), 98-105. An African-American reference Family Panel containing family histories and DNA samples is being built up in Howard University, Washington D.C.; Human Genome News 3: 4. The use of mitochondria to trace family histories and human evolution is discussed in NS (22 Feb 1992), 10, and a debate on human origin theories between the single Eve idea (we all evolved from an African mother 200,000 years ago) versus longer separation is in SA (April 1992), 98-105.
An orchid gene repository is being established; Science 255: 1359. The rice genome project in Japan is advancing; Nature 356: 181. Recently, researchers identified a gene determining whether rice will be fluffy or not, which is important for taste.
Scientific papers on the topic include: J. Sulston et al., "The C. elegans genome sequencing project: a beginning", Nature 356: 37-41, 14-5. Comment on the commercialisation of the C. elegans sequencing (EEIN 2: 25) are in Science 255: 677-8. The use of dyes and mass spectrometry is being advanced as an idea for speeding up gene sequencing, and electron micrographs of base pairs of DNA are shown in NS (29 Feb 1992), 19.
The debate over the patenting of cDNA sequences was discussed above, in the patenting
section. European scientists have called for a treaty on human gene patents, and
have stopped sending their sequence data to the UK MRC gene sequence database; Science
256: 727; NS
(9 May 1992), 5, NS
(11 April 1992), 7. In the UK a new genome center may be established, with funding by
the Welcome Institute; NS
(16 May 1992), 7; Nature
357: 99. Industrial methods to map DNA are discussed in Science
256: 463; Biotechnology
10: 478, 80.
As discussed in the patent section, Jim Watson quit as head of the NIH Genome Project; Science 256: 171, 301-2, 956-8; Nature 356: 463, 569; BMJ 304: 1132-3. Canada has begun a genome project, joining the US, France, Britain, Germany, Europe, Japan and South Korea; Nature 357: 428; Science 256: 1514. It has commited C$22 million over the next five years. A total of 7.5% of the funds will be devoted to ethical, social and legal issues (ELSI), much more than in other countries. In Japan the total to be spend on ELSI studies in 1992 is about 10 million (the same for the next five years), a very small total (about US$85,000).
The concentration of genes along the chromosomes is not uniform, the highest concentration is reportedly in the telomeric bands of metaphase chromosomes; PNAS 89: 4913-7. The use of sequence tagged sites for genome mapping is discussed in PNAS 89: 3681-5. However, French researchers have released a complete map of chromosome 21, using YACs and they estimate that 90% of the human genome can be mapped by the end of 1992, but it will take longer for the rest. The used a total of 250 megaYACs to map chromosome 21, and estimate a total of 30,000 YACs will be needed for the whole chromosome; NS (23 May 1992), 3, 5. On human genetics and geography see Nature 357: 284-5, 326-9, 329-33, 440-1; PNAS 89: 2277-81; JAMA 267: 2158.
Progress on the mouse genome project is summarised in HGN (March 1991), 6-7. The yeast genome project is progressing well, with the sequencing of an entire chromosome, Nature 357: 13, 38-46, see also Science 256: 462, 730. The cDNA sequencing of C. elegans , the nematode, is in Nature Genetics 1: 79-80, 114-31. The use of fingerprinting analysis in birds is discussed in Heredity 68: 481-94. Relating to plant genome data see Theor. Applied Genetics 83: 931-39; Genome 35: 171-81; and on the costs of DNA sequencing see Nature 357: 106, where an estimate of US$1 per base is made, for one project, and US$3 per base for another project. Finding errors in DNA sequences is described in PNAS 89: 4698-702.
A review of the Houston conference (EEIN 2: 29-30) is in Nature Genetics 1: 77-8. Related to the information arising from the Human Genome Project, some say that society is not ready for the results; NS (2 May 1992), 9; Science 256: 549-50; BMJ 304: 1187-8. A review of human genome research in Europe by W. Bodmer is in Science 256: 480-1.
The NIH patent application debate is commented on in the patents section above.
The scientist involved, Craig Venter, has left the NIH devoted to begin a non-profit
genome research institute, that is funded by a new company 'Human Genome Sciences
257: 151-2; Nature
358: 95. Other companies may be reluctant to enter the cDNA sequencing area because
the task should be completed within a short time; Nature
358: 180. A French project,
, is taking the lead in genome mapping, though it is the world's largest gene mapping
357: 526-7. A human genetic map is expected to be 90% complete by the end of 1992.
It uses automatic robotic analysis systems. Scientists attending the first North-South
Human genome Conference in Caxambu, Brazil, emphasised the need for sharing the results of the project, and we hope that government policy makers and lawyers will agree
with their statements. A new center in Cambridge, U.K. is being funded by the Welcome
Trust, to be called the Sanger Center; NS
(1 Aug 1992), 12-3; Science
The Canadian genome research program may be about C$60 million over 5 years, including 7.5% on ELSI issues; Lancet 339: 1530. An English-language review of H.-M. Sass (ed.), Genomanalyse und Gentherapie. Ethische Herausforerungen in der Humanmedizin (Berlin: Springer 1991, 347pp, DM98) is in Bioethics 6: 177-80; see also J. Medical Ethics 18: 107. A review of Code of Codes, is in Science 257: 981-2; also for a related book review see J. Medical Ethics 18: 109-10.
The success of genome studies on the nematode worm, C. elegans , (EEIN 2: 40), are commented on in Human Genome News 4 (May 1992): 1-2. Sequences and a report on the project on the bacteria E.coli are published in Science 257: 771-8. A status report of the genome sequencing in model organisms is in Biotechnology 10: 760-1. As of June 4, 1992 from the EMBL databank, 76% of the E.coli genome had been sequenced, 27% of S. cerevisiae (yeast), with 0.6% of the human sequence deposited. On sequence determination and probing see Biotechnology 10: 757-8. On the mouse genome map from the mouse project see Genetics 131: 423-47; Lancet 339: 1534. Analysis of the composition and function of yeast proteins is in Nature 358: 287; and on the relationship of new gene sequences reported from yeast and C. elegans to older sequences, Nature 357: 543-4. A proposal for gene mapping is J.F. Sabl & C.D. Laird, "Epigene conversion: a proposal with implications for gene mapping in humans", AJHG 50: 1171-7.
The resignation of J.D. Watson as director of the NIH NCHGR is reported in Human Genome News 4 (May 1992), 3; and discussed in GEN 12(7), 3, 24. The reporting of his resignation by Human Genome News is criticised as propaganda in Nature 357: 524. A review of the project is E. Jordan, "The Human Genome Project: Where did it come from, where is it going?", AJHG 51: 1-6.
A report on the activities of a NIH-DOE task force on genetics and insurance is in Human Genome News 4 (May 1992): 6-8. Criticism of the project is in A.I. Tauber & S. Sarkar, "The Human genome project: has blind reductionism gone too far?" Perspectives in Biology & Medicine 35: 220-35. General US government science funding is discussed in Science 257: 157-8, noting that the SSC project has not been funded. A book review of interest, Big Science, is in Science 257: 110-1.
The software and informatics retrieval systems in the USA and the involvement of the National Center for Biotechnology Information is discussed in Science 257: 156-7. On statistical analysis of sequence see S. Karlin & V. Brendel, "Chance and statistical significance in protein and DNA sequence analysis", Science 257: 39-49. Sequence analysis methods are discussed in Biotechnology 10: 751-5. See also a book review in Biotechnology 10: 772.
The structure of DNA can be examined over longer range regions, and there are some correlations extending over long range found already; Nature 358: 103. The unstable properties of DNA are discussed in AJHG 51: 7-9.
The issue of cDNA
was discussed in the patents section. Papers on the commercialisation of the human
genome, in French are in the Lettre du Comite Consultatif national d'ethique pour les sciences de la vie et de
(March 1992), 16 page supplement.
A series of commentary papers from a conference organised by the Hastings Center, the Genetic Prism, on ELSI issues is in a 16 page Supplement to the July/August issue of the Hastings Center Report. There are also book reviews of T.F. Lee, The Human Genome Project, and S. Krimsky, Biotechnics and Society, on p. 38-9. Reports on the ELSI programs of the US DOE and NIH are in Human Genome News (July 1992), 1-4. A bibliography of 2400 papers, books and articles on the ELSI issues of the Human Genome Project has been prepared by Michael Yessley, contact him Fax Int+1-505-665-4424, at the Los Alamos National Laboratory, New Mexico. The database is on-line and updated and searches on particular topics can be made.
Physical chromosome maps (overlapping cloned pieces of the complete chromosome) of two chromosomes have been published recently; I. Chumakov et al., "Continum of overlapping clones spanning the entire human chromosome 21q", Nature 359: 380-7; for the Y-chromosome see Science 258: 52-60. For a general review of the approaches see Nature 359: 367-8; Science 258: 11. Meanwhile, researchers in France describe improved techniques which means we can approach mapping by looking at the whole human genome, not individual chromosomes; C. Bellanne-Chantelot et al., "Mapping the whole human genome by fingerprinting yeast artificial chromosomes", Cell 70: 1059-68. The French genome project is discussed in Science 258: 28-30; and the Genethon center is described in Science 257: 1856-7. A method for DNA sequencing is reviewed in R.A. Mathies & X.C. Huang, "Capillary array electrophoresis: an approach to high-speed, high-throughput DNA sequencing", Nature 359: 167-9. Letters on computer speed for sequence comparison are in Science 257: 1609-10. On the automated approach see GEN (1 Oct 1992), 8-9.
The current (published that is!) status of the genetic mapping is reported in NIH/CEPH Collaborative Mapping Group, "A comprehensive genetic linkage map of the human genome", Science 258: 67-86, 148-62. X-chromosome analysis is described in Science 258: 103-10, and 40% is already in physical cloned maps.
The construction of a YAC library for 30% of the model plant organism, Arabidopsis thaliana , is reported in Aust. J. Plant Physiology 19: 341-51. A conference report on scanning probe microscopy is in Lancet 340: 600-1. These microscopes have a magnification of 100 million times and resolution of one-hundredth of the diameter of atoms and can be used on living cells or molecules. People interested in the Japanese rice genome project (China also has announced a project) can receive a newsletter, Rice Genome, contact Rice Genome Research Program, National Institute of Agrobiological Resources, 2-1-2 Kannondai, Tsukuba, Ibaraki 305, Japan (FAX +81-298-38-7468).
Papers on the science aspects, include a review on the Alu PCR system for identifying DNA fragments in Human Genome News (July 1992), 6-7. The long range construction of DNA and the similarity to fractals (from chaos theory) are discussed in SA (Sept 1992), 13-4. Of related interest is a question in molecular biology about the reason why there are exons and introns, see H.M. Seidel et al., "Exons as microgenes?", Science 257: 1489-90; R.F. Gesteland et al., "Recoding: reprogrammed genetic decoding", Science 257: 1640-1.
An editorial on US research funding and NASA projects calls for the space station project to stop; Nature 358: 609. Another editorial asks whether research benefits can be proved, looking at the US budget Nature 359: 173-4. Japanese science budgets may be increasing next year, Nature 359: 96. Japan is giving US$600,000 to the Genome Data Base in Baltimore; NS (29 Aug 1992), 6. This is still less than half of the European contribution, but a good sign.
Research on the genetic diversity and relationships of human beings is described in Science 257: 1204-5. Researchers are making a list of 400 populations to sample, and take about 25-50 individual samples from each of these. Research on Indo-European migration is reported in R.R. Sokal, et al., "Origins of the Indo-Europeans: Genetic evidence", PNAS 89: 7669-73; Science 257: 1346. They find that neither of the current major hypothesises on the origin of this broad group are supported by genetic data, and a further model is required. A review of the study of the 5,300 year old ice man is in Time (26 Oct 1992), 44-51.
A sample of 30 million year old DNA has been analysed, and described in R. DeSalle et al., "DNA sequences from a fossil termite in Oligo-Miocene Amber and their phylogenetic implications", Science 257: 1933-6, 1860-1. This is the oldest DNA yet analysed; NS (17 Oct 1992), 15. The use of genetic studies to look at the relationships and evolution of animals and plants is described in papers, A. Cooper et al., "Independent origins of New Zealand moas and kiwis", PNAS 89: 8741-4; "Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting", PNAS 89: 8611-5; J. Bousquet et al., "Extensive variation in evolutionary rate of rbcL gene sequences among seed plants", PNAS 89: 7844-8. A theoretical model of the selection of DNA bps in gene-regulatory binding sites is tested in E.coli in PNAS 89: 7501-5.
Further on the newly founded Genomic Research Institute that Dr C. Venter is directing (EEIN 2: 67) is in GEN (Aug 1992), 1, 22. He estimates that during the last two years at the NIH they identified 8,000 human genes. They expect to sequence about 2,000 to 3,000 genes per week, so that the cost falls to about $US$20 each, from the current US$40,000 per gene. The genome project should be completed very soon. The representatives of the new institute say that they will not apply for broad patents, but intend only to apply for patents on a few key genes with suggested utility, and will publish results within 6 months of discovery; Science 257: 1620.
A general review of the issues raised by the HGP from a Christian viewpoint is J.
and Christian Belief
4(2), 105-25. A conference report from an April conference "The Genie in the Genome"
is in Human Genome News
(Sept 1992), 12. HUGO has reestablished an ethics committee chaired by Victor McKusick,
Alain Pompidou and Nancy Wexler, and they had a meeting 9-11th October in Amsterdam.
A review of the Second International Fukui Bioethics Seminar (see the books Human Genome Research and Society advertised on back page) by N. Fujiki and D. Macer is in Int. Digest of Health Legislation 43: 660-2. A review of G.J. Annas & S. Elias, eds., Gene mapping: Using Law and Ethics as Guides (Oxford Univ. Press 1992, 291pp., US$40) is in Nature 360: 380-1. A report of a British meeting is in JRSM 85: 710-1. A letter urging people to reveal possible sources of conflict (e.g. monetary interest) is in AJHG 51: 1168. A book review of R. Shapiro, The Human Blueprint: The Race to Unlock the Secrets of Our Genetic Script (London: Cassell, 412pp., 17) is in BMJ 305: 1032-3. A critical paper by A. Lippman says that the emphasis placed on the genome project may have negative eugenic effects on society and health care; SSM 35: 1469-76.
Anthropologists are joining the human gene diversity study; Science 258: 1300-1. A paper describing some aspects of the frozen ice man found in the European Alps is H. Seidler et al., "Some anthropological aspects of the prehistoric Tyrolean Ice man", Science 258: 455-7. Some comments on the history of human anthropology are in AJHG 51: 913-5; SA (Nov 1992), 17; linguistic origins of Native Americans, SA (Nov 1992), 60-5; human language origins as a means of societal tolerance, NS (21 Nov 1992), 28-31; chemical evidence for ancient beer, Nature 360: 24; Saharan agriculture using sorghum and millet 8,000 years ago, Nature 359: 721-4.
A new linkage map of the human genome is in J. Weissenbach et al., "A second-generation linkage map of the human genome", Nature 359: 794-801. The average resolution is 5cM. A review of the progress in the genome project, which predicts a completion date of 1999 for the complete sequence is Nature 359: 777-8; BMJ 305: 851. The USA is setting up a large genome mapping centre, modelled off the success of the French centre; Nature 360: 401. As reported in EEIN 2: 72, they use a whole genome approach rather than focusing on individual chromosomes. A nomenclature for pieces of the genome is suggested in PNAS 89: 10706-10, based on using the pot ential gene idea to call units potonuons and potogenes. The computer analysis of long distance patterns in DNA sequence is reported in Science 258: 895; Nature 359: 782. A microscopic technique for sizing single DNA molecules is reported in Nature 359: 783-4. A review on how to visualise biomolecules is in SA (Nov 1992), 44-51. Gene research on Dictyostelium is discussed in Science 258: 402-3.
The EC has joined the USA and individual European countries in declaring this a decade of brain science research; Science 258: 23, 387. The 9th October issue of Science features brain science papers. On the neocortex see Science 258: 237-8; circadian rhythms, p. 238-40; glutamate, p. 241-3; learning, p. 243-5; memory, p. 245-6; self-remapping of the brain, p. 216-8. See also two 8 page supplements to New Scientist (14 Nov 1992), (28 Nov 1992).
A description of how the decisions on how the recent US$210 million extra funding for breast cancer research will be spent in the USA is in Science 258: 732-4. It also discusses women's health issues. A history of pre-Meiji era science in Japan by the Emperor Akihito is in Science 258: 578-80. Remarks on basic science funding in the USA is Science 258: 200-1, 880-2; and on public or private research in Japan; Science 258: 582-3.
As of October 1992, the US-located international GenBank Genetic Sequence Database
contained 100 million DNA nucleotides, increased from the 1991 data of 40 million
nucleotides. The site of a new European animal and human genome sequence database
is being debated; Nature
361: 383. The new "European Bioinformatics Institute" may be situated in Heidelberg
or Cambridge. The problems of organising a European Community human genome project
meeting are described in Biotechnology
A review of the commercial investment into the genome project and issues it raises is in Science 259: 300-2. Time magazine (8 Feb 1993), 43, has said that the French genome project is on higher moral ground than the US project, because it is donating the results to the UN and is not seeking gene patents. In addition, the US has started to adopt the French scientific approach, focusing on the whole genome rather than individual chromosomes; Science 258: 1573.
Two conference reviews on ethics of genetic technology and the genome project are in Human Genome News (Nov 92), 12-3. The U.K. genome project is discussed in Nature 361: 387. The appointment of a new director for the NIH genome project is discussed in Science 258 (1992), 1723; Francis Collins has verbally agreed to start in March; Science 259: 22. Thomas Caskey has been appointed new president of HUGO; Science 258 (1992), 1575.
A list and map of human diseases mapped onto the genome is reviewed in V.A. McKusick & J.S. Amberger, "The morbid anatomy of the human genome: chromosomal location of mutations causing disease", JMG 30: 1-26. A review of mapping progress is in SA (Jan 1993), 7-9. Scientific papers include: N. Lisitsyn, "Cloning the differences between two complex genomes", Science 259: 946-51; Nature 360 (1992), 606-10. An automated method to generating expressed sequence catalogues is reviewed in Nature 361: 375-6. A review of genomic DNA sequencing is in Biotechnology 11: 39-42.
The problems and progress towards a brain data base are reviewed in Science 258 (1992), 1872-3; Nature 361: 109-20. The choice of a male and female to be the basis for digitalisation is being made; SA (Jan 1993), 122-3. However, don't offer, because the brain must be dead.
The origin of the different human races is discussed in NS (16 Jan 1993), 34-7; Science 259: 639-46; Nature 361: 314; SA (Dec 1992), 16; M.W. Feldman & L.A. Zhivotovsky, "Gene-culture coevolution: Toward a general theory of vertical transmission", PNAS 89 (1992), 11935-8. A map of the relations between 24 tribes from America is discussed in Science 259: 312-3. Some DNA samples from the Austrian fossil "iceman" have begun analysis in Munich; Science 258 (1992), 1871. The ethical implications of the project and policy suggestions are made by C. Byk, "The human genome project and the social contract: A law policy approach", J. Med. & Phil. 17 (1992), 371-80.
The NIH and DOE have released guidelines encouraging the
of data and resources, and stipulating that researchers who receive funds should
publish (and deposit) data within 6 months of discovery; Human Genome News
(Jan 1993), 4.
A review of a US meeting of ELSI grantees is in Human Genome News (Jan 1993), 5-6. They suggested the key areas for further research include client-centered assessments of new genetic services and technologies, education, and interpreting genetic variation. A review of the policies developed for genetic family studies is on p. 7, 9. A new report on ethics and the genome project is The Danish Council of Ethics, Ethics and Mapping of the Human Genome, 86pp (see address in bioethics centres list). It includes issues such as protection of sensitive personal information, genetic screening and testing. A commentary looking at discrimination is B. Muller-Hill, "The shadow of genetic injustice", Nature 362: 491-2. A philosophical paper on determinism is P.S. Greenspan, "Free will and the genome project", Phil. & Public Affairs 22: 31-43.
Craig Venter has reported at a US conference on the 1st April that they may have listed 95% of all the human genes by 1994 . This may affect policy regarding funding the rest of the genome project, and calls in an editorial in Nature for the importance of both approaches are made; Nature 362: 488, 575-6.
Reviews of the fortieth anniversary of the DNA double helix paper are in Science 259: 1532-3; Time (15 March 1993), 40-3; JAMA 269: 1040-5; Nature 362: 105.
On the scientific project, details of the NIH-genome center in MIT, USA, are in Human Genome News (Jan 1993), 8. The projects include continuing the work of the French Genethon genome mapping group (Daniel Cohen is also involved in MIT). A review on the long fragment YAC library made in France is in Science 259: 1684-7. Another scientific center is being set up in the NIH headquarters, for the new program director, Francis Collins; Nature 362: 581. The new lab will target medical applications; Science 260: 152-3. The UK is also focusing on two large new medical centres; NS (13 Feb 1993), 7.
Progress on the genetic mapping of behavioural genes in dogs is reported in BioScience 43: 7. The dog genome is about the same size as humans, and there are 40 chromosomes. Initially 400 markers will be found. A genetic project on racehorse genetics is discussed in Science 259: 1823, though a lack of money has postponed it. The evolutionary relationships among whale species are being redrawn following gene mapping studies; NS (20 Feb 1993), 15. The automation in the C. elegans genome sequencing project is reported in Nature 362: 569-70.
Reports on the frozen Austrian iceman are in Nature 362: 11-2, and on general evolutionary studies JAMA 269: 1477-8, 80. The global human genetic diversity project, involving samples from 400 tribes around the world, is discussed in Nature 361: 675. Part of a homeobox gene complex in a 30 million year old fossilised insect has been isolated, and is being analysed in a Japanese laboratory. It follows other studies published last year on DNA analysis from similarly old samples (EEIN 2: 82). A paper estimating that there are less than 900 ancient conserved regions in all genes is P. Green et al., "Ancient conserved regions in new gene sequences and the protein databases", Science 259: 1711-6; 942-3. A report of contamination of cDNA sequences in databases with nonhuman DNA is in Science 259: 1677-8. The use of magnetic bead capture of expressed sequences is reviewed in Nature 361: 751-3.
The brain mapping project is discussed in Newsweek (26 April 1993), 52; JAMA 269: 1357. Computing and DNA analysis is discussed in Biotechnology 11 (March 1993), S9; Nature 361: 484; see also, AJHG 52: 442-3. Cambridge is the new site for the improved EMBL genome database; Science 259: 1527; Nature 361: 198.
There were numerous anniversary papers celebrating the 40th anniversary of the DNA
structure paper. To add to the list see general papers on genome projects, gene
therapy and transgenic organisms in NS
(24 April 1993), 21-41; Nature
362: 783; JAMA
269: 1981-5, 1993-4. Book reviews on human genetics and social issues are in JAMA
269: 2003-7. A review of the human genome project by M.V. Olson is in PNAS
A listing of the US Genome Centers, their major goals and accomplishments, and resources is in Human Genome News (March 1993), 2-9. The 1994 Fiscal year NIH proposal for the genome project is to increase from 107 to 135 million US dollars; GEN (1 May 1993), 3. Breast cancer research may increase from 206 to 422 million dollars in FY 1994. On European genome research see Science 260: 1740-2.
A letter on the megaYAC library from France is in Science 260: 877; and on database contamination see Science 260: 605-7. A commercial deal to market genes and products of the company Human Genome Sciences Inc. is reported in Nature 363: 387. It includes the company SmithKline Beecham, in a world-wide marketing rights deal worth US$100 million. Cosmid maps of the yeast Saccharomyces pombe are in Cell 73: 109-20, 121-32.
A new technique called genomic mismatch scanning (GMS) increases the speed at which linkage mapping of multigene traits can be performed; GEN (1 Jun), 1, 19. The whole genome can be examined by hybridisation after first fragmenting it. A Stanford University group has used the technique in yeast, and it also works in humans. It is being commercially developed. Another techique is sequencing by hybridization (SBH) for large scale sequencing, Science 260: 1649-52. On the progress for completely automated sequencers using primer walking that would revolutionise sequencing see Science 260: 1075. A procedure for cDNA maps is R.Das Gupta et al., "An integrated approach for identifying and mapping human genes", PNAS 90: 4364-8.
As reported above, the movie Jurassic park has been a success. A scientific paper reporting the sequencing of genes from a 120 million year old insect shows that part of the idea is feasible - off course not the whole genome!; R.J. Cano et al., "Amplification and sequencing of DNA from a 120-135 million year old weevil", Nature 363: 536-8.
A review of the human genetic diversity project is NS (29 May 1993), 25-9. Genetic studies on human diversity include, PNAS 90: 4670-3; AJHG 52: 846-7; Annals of Human Genetics 57: 55-64. A report on gorilla genetics shows that they are very diverse and may be actually 2-3 subspecies; Science 260: 893. On why we walk on two legs and comparison to primates see Nature 363: 587-8.
The US Army received a US$210 million grant to fund breast cancer research, as discussed previously. It has used peer review and US151 million of the grants will be similar to NIH investigator-led grants; Nature 363: 195; Science 260: 1068; JAMA 269: 2417. Also on women's health issues and increased funding; Science 260: 744-6; Nature 363: 99-100, 383. A reshaping of UK science is reported in Nature 363: 287, 381-2; BMJ 306: 1498-9.
The conclusions of the
working group of the
are in BME
(June 1993), 10-11. A series of papers on the ethics issues of the genome project in
French is M.J. Melancon & R.D. Lambert, eds. Le Genome Humain. Une Responsibilite Scientifique et Sociale,
published by Les Presses de L'Universite Laval 1992,180pp. Academic papers on ethics
and genetics in French are also in IJB
4: 111-9;121-4. Book reviews of Gene Mapping: Using Law and Ethics as a Guide
11: 837; AJHG
Canada's role in the project is reviewed in CMAJ 148: 1309-13, together with difficulties of introducing genetics into medicine. General book reviews are BMJ 307: 210; NEJM 329: 584-7. The gathering speed of cDNA gene cloning is discussed in Nature 364: 554, Nature Genetics 3: 189-91.
On the dog genome project and behavioural genetics studies, NS (26 June 1993), 5. Plant systematics and phylogeny using DNA analysis is reviewed in BioScience 43: 380-9; and plastid DNA trees are in Nature 364: 762-3. (Also see the section on Biotechnology and the Public, on dinosaurs). A suggestion that " junk " DNA may be to check the correct processing of genes is NS (26 June 1993), 15. Tracing the history of the immune system is discussed in Science 261: 164.
The Eye Research Institute of Canada in Toronto has become the world's first clinical diagnostic laboratory for automated DNA analysis; GEN (July 1993), 1, 15, 39. A report from the first International Symposium on the Mapping and Sequencing of Small Genomes is in GEN (Aug 1993), 34-5, 43. The BioInformatics Institute in Cambridge is discussed in TIBTECH 11: 217-8. An indexing method for faster searching of databases has been made, NS (7 Aug 1993), 20. Robotic methods are discussed in Biotechnology 11: 793-6; Science 260: 1649-52.
has announced a genome project, joining the list of countries with a formal genome
365: 200. China has 56 ethnic groups making it interesting to compile data from
such groups. On the economic problems in the
genome project see Science
261: 1382. The future plans for the French Genethon laboratory are reported in Nature
Several papers on DNA analysis of ethnic groups and use to trace relationships between human populations are in AJHG 53: 549-618. General comments on the use of DNA polymorphism for population studies are in PNAS 90: 7425-6. A review of the methods that allow extraction of DNA from ancient samples of fossils, and the problem of oxidation of DNA over time, is Nature 365: 700. A database of ancient DNA sequences is a recent addition to the range of databases available; Nature 364: 19-20. A general comment on the marriage of computers and biology is Nature 365: 9.
Commercial genome sequencing in the USA is receiving another US%125 million from Smith Kline Beecham, in an agreement with Human Genome Sciences, Biotechnology 11: 982. Further comments on commercial genome research, and the strategy of applying genes found by the project for use, GEN (15 Sept 1993), 1, 8, 29.
A review of parallel genome analysis by two-dimensional DNA typing is in Nature 365: 469-71. The system is partially automated.