Raymond Gosling: the man who crystallized genes

On April 25th 1953, three publications in Nature forever changed the face of the life sciences in reporting the structure of DNA. Sixty years later, Raymond Gosling shares his memories of the race to the double helix.It has not escaped our attention that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.James D Watson and Francis HC Crick [1]By including this statement in their April 25th 1953 Nature article describing a model for the structure of DNA, Watson and Crick made one of the great understatements in history. In that moment, the seeds for the double helix''s infamy - alongside the names ''Watson'' and Crick'' - were sown. Lesser known outside scientific circles is that this article did not include one iota of experimental data: Watson and Crick, who were based at the University of Cambridge''s Cavendish laboratory, contributed deductive reasoning alone to the double helix model, albeit reasoning of an undoubtedly Nobel Prize-worthy standard. Instead, as has now been described many times, the model relied on X-ray diffraction data obtained by others, at King''s College, and these data did not reach Watson and Crick by entirely wholesome means [2]. To add to the insult, Watson and Crick''s report of the double helix did not fully credit the work of King''s as being essential to the construction of their model, although the King''s team did enjoy co-publication of their data alongside the double helix article, in the form of two articles in the same issue of Nature [3,4]. One of these articles described the X-ray diffraction work performed by senior researcher Rosalind E Franklin, together with PhD student Raymond G Gosling, and contained the highest quality diffraction patterns yet achieved for DNA [3]. It was these data that had proved invaluable in Watson and Crick''s quest for the double helix.Earlier still, before Franklin arrived at King''s, Gosling had achieved a major breakthrough in the search for DNA''s structure when he became the first person to crystallize genes, under the guidance of Maurice Wilkins, who was the lead author of the other King''s article to accompany Watson and Crick''s model [4].Watson published his controversial memoir of the discovery, aptly named ''The Double Helix'', in the 1960s [5], and in doing so propelled the story to worldwide fame, establishing DNA''s structure as an icon of science in the popular imagination. However, events were relayed in Watson''s book very much from his own point of view and at times, it has been argued, even verged on the fictitious.Aside from Watson, Ray Gosling is the only surviving member of the select group of seven scientists to feature as an author on one of the three Nature articles. Gosling and his wife, Mary, were kind enough to welcome Genome Biology into their home, where he shared with us his perspective of the events of 60 years ago.Elsewhere, Genome Biology has marked the anniversary by canvassing our Editorial Board for their opinions on the most important advances in the field since 1953 [6].     

Will hospital closures mean physician unemployment in Ontario?

Dr. Duncan Sinclair, the former dean of medicine who heads the commission charged with restructuring Ontario''s health care system, said something dramatic was needed to revamp the system. He wasn''t kidding. His commission recently called for the closure of 3 hospitals in Ottawa and 10 more in Toronto. In a wideranging interview with Charlotte Gray he talks about the commission''s goals and their potential impact on physicians.     

Lessons my $3101 cat taught me about universal health care

Dr. Brian Goldman describes how his cat''s experience with veterinary medicine has helped shape his views about Canada''s health care system.     

An appreciation of A.E. Malloch,MB, MD (1844-1919): a forgotten surgical pioneer

Dr. Archibald Edward Malloch was a surgeon whose life and work were greatly influenced by Joseph Lister and his revolutionary system of antiseptic surgery. This paper describes how a young Canadian medical man came to introduce Lister''s system to North America in 1869 and studies his career in the light of Lister''s surgical epoch.     

Therapeutic antibody engineering

It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.     

1 July 1858: what Wallace knew; what Lyell thought he knew; what both he and Hooker took on trust; and what Charles Darwin never told them

At the Linnean Society on 1 July 1858, Charles Lyell and Joseph Hooker, using only an extract from Charles Darwin's unpublished essay of 1844, and a copy of a recent letter to Asa Gray in Boston, argued successfully that Darwin understood how species originate long before a letter from Alfred Russel Wallace outlining his own version of the theory of evolution arrived at Darwin's home. That letter from Ternate in the Malay Archipelago, however, was not the first letter Darwin received from Wallace. This article will contend that two of the three letters Wallace sent Darwin between 10 October 1856 and 9 March 1858 arrived much earlier than Darwin recorded, thereby allowing him time to assess Wallace's ideas and claim an independent understanding of how the operation of divergence and extinction in the natural world leads strongly marked varieties to be identified as new species. By the time of the Linnean meeting Darwin's new ideas had filtered into his letters and ‘big’ species book, despite the absence of any independent evidence from the natural world to justify his constant insistence to have been guided only by inductive reasoning. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109 , 725–736.     

His own private hospital

Dr. Brian Day had a simple solution when it became increasingly difficult to book operating room time in Vancouver. He built his own hospital. The Cambie Surgical Centre, which treats patients from BC and around the world, has 2 main operating rooms, 10 recovery beds and 5 private rooms for extended stays. "What I''ve done," says Day, "is say that if there are no operating rooms at UBC, I''ll build my own."     

Liver transplantation in 100 children: Cambridge and King's College Hospital series.

To review the results of the Addenbrooke''s and King''s College Hospital children''s liver transplantation programme.Retrospective analysis of the first 100 children to receive liver grafts at Addenbrooke''s Hospital, Cambridge, from December 1983 to March 1990.Addenbrooke''s Hospital, Cambridge, and King''s College Hospital, London.153 children assessed for liver transplantation, of whom 22 died before a donor became available and 31 were considered unsuitable. 100 children received grafts, of whom 27 had second grafts.One year actuarial patient survival was 71%, with 57% one year graft survival. In the last two years survival rates had improved considerably, with 86% of patients and 63% of grafts surviving for at least one year. Sixty five children were alive 12 to 86 months after transplantation; 63 were well and leading normal active lives and 56 had entirely normal liver function. Children''s growth and development were essentially normal, with many showing remarkable catch up growth.Liver transplantation offers children with terminal liver disease a high chance of a return to full quality life and normal development. Improved surgical and medical care have progressively improved survival. The timing of transplantation is critical but has been constrained particularly by the availability of donors and resources.     

The sacredness of human life

Christian De Duve''s decision to voluntarily pass away gives us a pause to consider the value and meaning of death. Biologists have much to contribute to the discussion of dying with dignity.Christian de Duve''s voluntary passing away on 4 May 2013 could be seen as the momentous contribution of an eminent biologist and Nobel laureate to the discussion about ‘last things''. In contrast to his fellow scientists Ludwig Boltzmann and Allan Turing, who had made a deliberate choice to end their life in a state of depression and despair, de Duve “left with a smile and a good-bye”, as his daughter told a newspaper.What is the value and meaning of life? Is death inevitable? Should dying with dignity become an inalienable human right? Theologians, philosophers, doctors, politicians, sociologists and jurists have all offered their answers to these fundamental questions. The participation of biologists in the discussion is long overdue and should, in fact, dominate the discourse.We can start from de Duve''s premise—expressed as a subtitle of his book Cosmic Dust—that life is a cosmic imperative; a phenomenon that inevitably takes place anywhere in the universe as permitted by appropriate physicochemical conditions. Under such conditions, the second law of thermodynamics rules—prebiotic organic syntheses proceed, matter self-organizes into more complex structures and darwinian evolution begins, with its subsequent quasi-random walks towards increasing complexity. The actors of this cosmic drama are darwinian individuals—cells, bodies, groups and species—who strive to maintain their structural integrity and to survive as entities. By virtue of the same law, their components undergo successive losses of correlation, so that structures sustain irreparable damage and eventually break down. Because of this ‘double-edge'' of the second law, life progresses in cycles of birth, maturation, ageing and rejuvenation.Death is the inevitable link in this chain of events. ‘The struggle for existence'' is very much the struggle for individual survival, yet it is the number of offspring—the expression of darwinian fitness—that ultimately counts. Darwinian evolution is creative, but its master sculptor is death.Humans are apparently the only species endowed with self-consciousness and thereby a strongly amplified urge to survive. However, self-consciousness has also made humans aware of the existence of death. The clash between the urge for survival and the awareness of death must have inevitably engendered religion, with its delusion of an existence after death, and it might have been one of the main causes of the emergence of culture. Culture divides human experience into two parts: the sacred and the profane. The sacred constitutes personal transcendence: the quest for meaning, the awe of mystery, creativity and aesthetic feelings, the capacity for boundless love and hate, the joy of playing, and peaks of ecstasy. The psychologist Jonathan Haidt observed in his book The Righteous Mind: Why Good People Are Divided by Politics and Religion that “The great trick that humans developed at some point in the last few hundred thousand years is the ability to circle around a tree, rock, ancestor, flag, book or god, and then treat that thing as sacred. People who worship the same idol can trust one another, work as a team and prevail over less cohesive groups.” He considers sacredness as crucial for understanding morality. At present, biology knows almost nothing about human transcendence. Our ignorance of the complexity of human life bestows on it both mystery and sacredness.The religious sources of Western culture, late Judaism and Christianity, adopted Plato''s idea of the immortality of the human soul into their doctrines. The concept of immortality and eternity has continued to thrive in many secular versions and serves as a powerful force to motivate human creativity. Yet, immortality is ruled out by thermodynamics, and the religious version of eternal life in continuous bliss constitutes a logical paradox—eternal pleasure would mean eternal recurrence of everything across infinite time, with no escape; Heaven turned Hell. It is not immortality but temporariness that gives human life its value and meaning.There is no ‘existence of death''. Dying exists, but death does not. Death equals nothingness—no object, no action, no thing. Death is out of reach to human imagination, the intentionality of consciousness—its directedness towards objects—does not allow humans to grasp it. Death is no mystery, no issue at all—it does not concern us, as the philosopher Epicurus put it. The real human issue is dying and the terror of it. We might paraphrase Michel Montaigne''s claim that a mission of philosophy is to learn to die, and say that a mission of biology is to teach to die. Biology might complement its research into apoptosis—programmed cell death—by efforts to discover or to invent a ‘mental apoptosis''. A hundred years ago, the micro-biologist Ilya Mechnikov envisaged, in his book Essais Optimistes, that a long and gratifying personal life might eventually reach a natural state of satiation and evoke a specific instinct to withdraw, similar to the urge to sleep. Biochemistry could assist the process of dying by nullifying fear, pain and distress.In these days of advanced healthcare and technologies that can artificially extend the human lifespan, dying with dignity should become the principal concern of all humanists, not only that of scientists. It would therefore be commendable if Western culture could abandon the fallacy of immortality and eternity, whilst Oriental and African cultures ought to be welcomed to the discussion about the ‘last things''. Dying with dignity will become the ultimate achievement of a dignified life.     

McMaster's pioneer in evidence-based medicine now spreading his message in England.

Dr. David Sackett, formerly of McMaster University and now at Oxford University in England, is considered one of the pioneers of the evidence-based medicine movement. This article looks at his colleagues'' assessment of Sackett''s contributions to medicine and at Sackett''s own views on his lengthy career.     

The National Forum reports: Crisis? What crisis?

The National Forum on Health''s final report appears to have said what Canadians--and the federal Liberal government wanted to hear about the health care system. It called for preservation of the single-payer model and the 5 principles of the Canada Health Act, and also recommended that medicare be expanded to embrace pharmaceuticals and home care. Edmonton internist Tom Noseworthy, chair of the forum''s steering committee, said public anxiety about medicare is caused by the rapid pace of change, not its direction. However, the CMA''s Dr. Judith Kazimirski was quick to challenge Noseworthy and his criticism of those who say a crisis exists.     

The World Health Organisation. Interview with the director general. Interview by Fiona Godlee.

Dr Hiroshi Nakajima was elected director general of WHO in 1988. Born in Japan, he trained as a psychiatrist before joining WHO in 1973. He was WHO''s regional director for the Western Pacific from 1979 to 1988. His term of office has been marked by criticism of his management style and allegations of misuse of WHO''s funds. I spoke to him at WHO''s headquarters in Geneva in July. I have presented the interview in the form of questions and answers. It would be misleading, however, not to make clear that in doing so I have transcribed conversation which was at times extremely difficult to follow. I feel that it is important to emphasise this in the context of an interview with an international leader, one of whose primary tasks must be to communicate his views on health to people across the world. The interviews gave me first hand experience of the difficulties in communication that staff, diplomats, and others, including Japanese leaders, have consistently commented on since Dr Nakajima took office.     

1 July 1858 and the 1844 essay: what Lyell and Hooker decided; and what Darwin did not want and did not know

Two ‘papers’ of Darwin's were read at the famous 1 July 1858 meeting of the Linnean Society: an excerpt from his 1844 essay and a summary of his theory, enclosed in an 1857 letter to Asa Gray. Quite apart from not selecting the essay excerpt, Darwin's letters appear to indicate that he definitely did not want, and hence did not expect, an excerpt from his 1844 essay to be included (and that he did not learn of its inclusion until some 2 weeks after the meeting). As a result, we refine Darwin's role in ‘the delicate arrangement’, as well as the basis for Hooker's and Lyell's. In particular, why did they choose an essay excerpt to be presented contrary to Darwin's wishes? In direct opposition to the popular view, the essay excerpt was the afterthought, the last‐minute add‐on, not the enclosure to the Gray letter.     

Did Osler suffer from "paranoia antitherapeuticum baltimorensis"?: A comparative content analysis of The Principles and Practice of Medicine and Harrison's Principles of Internal Medicine, 11th edition

One of the most important legacies of Sir William Osler was his textbook The Principles and Practice of Medicine. A common criticism of the book when it was first published was its deficiency in the area of therapeutics. In this article, the 1st edition of The Principles and Practice of Medicine is compared with the 11th edition of Harrison''s Principles of Internal Medicine. The analysis focuses on the treatment recommendations for 4 conditions that were covered in both books (diabetes mellitus, ischemic heart disease, pneumonia and typhoid fever). Osler''s textbook dealt with typhoid fever and pneumonia at greater length, whereas Harrison''s placed more emphasis on diabetes mellitus and ischemic heart disease. Notwithstanding Osler''s reputation as a therapeutic nihilist, the 2 books devoted equivalent space to treatment (in terms of proportion of total sentences for the conditions). For all conditions except ischemic heart disease, Osler concentrated on general measures and symptomatic care. Throughout Osler''s textbook numerous negative comments are made about the medicinal treatment of various conditions. A more accurate statement about Osler''s therapeutic approach was that he was a "medicinal nihilist." His demand for proof of efficacy before use of a medication remains relevant.     

Toronto centre hopes to cash in on growing demand for private health services

When the CMA held its 1996 annual meeting, part of the debate on the future of health care involved the "appropriate balance of the roles of the public and private sectors" in delivering health care. The King''s Health Centre in Toronto is now doing its own balancing act: providing publicly funded care to Canadians, and private care to non-Canadians and Canadians who can afford it. This article discusses some of the niche markets King''s is attempting to develop.     

Requests approaching 50,000 annually for emergency drug release program.

Health Canada''s Emergency Drug Release Program, which allows physicians to acquire nonmarketed drugs to treat people with HIV infection, AIDS and other illnesses, handles about 44 000 requests annually. The executive director of the Drugs Directorate says the program''s name is a misnomer, since few of the requests involve medical emergencies. Dr. Philip Berger, who uses the program for his AIDS patients, complains that the amount of paperwork required is oppressive. A government spokesperson says changes may be made to make the program less labour intensive.