Thursday, October 7, 2010

Robert Edwards: The father of test tube babies

Now his work has been widely recognized and utilized, leading to four million lives that would not come at all without his work, although the church still criticizes him. It reminds how hard for new things to develop. It is the normal minds, which makes the biggest number, that impedes the few great ones. When new things come, these mediocre automatically try to crush them, rather than to rethink about their current situations and see if they can adapt. Such intolerance must have painful to Edwards.

Very few scientists can say that four million people are alive because of their work, but Robert Edwards is one of those few. His development of the technique at the heart of that claim — in vitro fertilization (IVF) — has won him this year's Nobel Prize in Physiology or Medicine.

To make IVF possible, Edwards had to solve numerous problems in basic biology — some of which opened the door for embryonic stem-cell research — while facing bitter opposition from churches, politicians and even some of his eminent colleagues at the University of Cambridge, UK. An outgoing yet thoughtful personality who eagerly engaged in public debate, Edwards was hurt by charges that his work was unethical.

But thanks also to his collaboration with another outsider, Patrick Steptoe, an obstetrician at the Oldham and District General Hospital, the world's first test-tube baby, Louise Brown, was born in 1978. Within five years, 150 test-tube babies had been born worldwide. Since then, IVF has become mainstream, and Edwards and Steptoe have been lauded for helping give life to millions. Had he not died in 1988, Steptoe would probably have shared the prize.

In 2001, Edwards won a Lasker award, which often presages the Nobel. Two years ago he celebrated the 30th anniversary of IVF at a symposium where the impact of this work on many levels of society — biology and medicine, but also law, ethics, the arts and social anthropology — was discussed. At 85, Edwards is now too frail to give interviews, but his wife told the Nobel Foundation of his happiness at receiving the prize. "No other scientist could have transformed so many aspects of our society," says Martin Johnson, one of Edwards's first graduate students and now professor of reproductive sciences at the University of Cambridge.

Edwards began his research career in the early 1950s working on the reproductive biology of mice. After harvesting eggs from female mice, he learned how to coax them, and eggs from other species, to mature and be fertilized in a test tube. He also worked out how to control the timing of the rodents' ovulation — which annoyingly tended to happen at night — by administering certain hormones.

Soon after he joined the National Institute for Medical Research in London in 1958, Edwards began applying his findings, and those of other groups working on reproductive biology, to humans. He acquired slices of human ovaries from surgeons, and from these he isolated immature eggs. He spent two disappointing years failing to coax them to mature in vitro, until he realized that the process required at least 24 hours of incubation, not the 12 hours that rodent eggs required. "It is these empirical observations that move science forward," says Ian Wilmut of the MRC Centre for Regenerative Medicine at the University of Edinburgh, UK, who also had to modify the conventional timing of cell incubation to create the first cloned mammal, Dolly the sheep. "These things seem very small in retrospect, but they are critical."

By 1968, Edwards had fine-tuned the maturation of human eggs, learning how to fertilize them with the potential father's sperm and to prod them into forming embryos that could be implanted. Having moved to the University of Cambridge he needed a collaborator to help him apply these techniques in human patients. Having read about Steptoe's pioneering work on laparoscopy — the placement of a fibre-optic endoscope into the abdomen to view internal organs — in his small hospital in northern England, Edwards picked up the phone. Steptoe was already using the method to withdraw fluid from the reproductive tract and agreed that he could also use it to extract eggs. Working as equal partners, the pair set out their own ethical guidelines, agreeing to stop if patients or children were endangered, but not in deference to what Edwards called "vague religious or political reasons".

The UK Medical Research Council refused to fund their work, believing it could lead to babies with severe abnormalities, and disapproving of the pair's high profile in the media (M. H. Johnson et al. Hum. Reprod. 25, 2157–2174; 2010).

Johnson recalls the "strange atmosphere" in the 1960s and 1970s, when the prospect of overpopulation seemed to be a bigger societal concern than infertility. "There was no awareness then of the personal pain of infertility," he says. "I remember eminent Cambridge scientists would tell us that our PhD supervisor was off his rocker." He also recalls Max Perutz and James Watson, both Nobel laureates at Cambridge, telling him it was irresponsible to interfere with the beginning of life. "Often people refused to speak to us in the tea room because they disapproved of what we were doing." Johnson stuck by Edwards though, finding him "inspirational and visionary".

The technique has not only benefitted infertile couples — it can also help parents to avoid passing on serious inherited diseases such as cystic fibrosis or Huntington's disease to their children, by selecting embryos that are free of dangerous mutations for implantation.

In addition, it has enabled the field of human embryonic stem-cell research. Reproductive biologist Outi Hovatta of the Karolinska Institute's IVF clinic in Stockholm, where new human embryonic stem-cell lines are derived from spare embryos, says that Edwards was the first, in 1984, to publicly discuss the benefits of such cells to medical research, and the ethical dilemmas that would inevitably accompany them. He was equally prescient on the need for oversight of his powerful technique, advocating in 1971 that a legal authority should be established to control IVF. The UK Human Fertilisation and Embryology Authority was founded 20 years later.

Scientists need a shorter path to research freedom

Usually a young needs to go through all the stages to arrive at its final intellectual autonomy, from undergrad, to PhD (sometimes even Mphil beforehand), and postdoc training. All these may take him around 15 years, which is very long and too long for the most gifted young who are highly creative and confident and motivated. Full pursuit freedom is quite essential to astounding ingenious findings. Einstein is the example. He acquired his independence by his uncompromisable desire for intellectual liberty and unbounded curiosity. Nothing could stop him from his zealous investigation. However, not all have his luck: he is with a incredibly strong heart that stems from his unfathomable passion and could overcome any balk ahead. Many young are talented but somewhat not that talented. They need a smoother academic environment to release their energy, or they would be throttled.

Nature 467, 635 (2010)

Over the past half-century, a great many things have changed in biomedical research. Along the way, postdoctoral training has become an established step in a research career. But this development has proved a double-edged sword for some — and possibly for the whole field.

Without question, postdoctoral training has enriched the experience of many by allowing protected time for full immersion in research. Postdocs provide essential skills and serve as first authors on many important papers, thus boosting research productivity. But these gains must be set against the significantly longer time it now takes for most young scientists to launch independent research careers. The average age of PhD scientists awarded their first research grant from the US National Institutes of Health (NIH) last year was 42. In 1981, the average was 36. As director of the NIH, I believe this is a problem that should be addressed. We must develop ways to liberate our brightest minds to pursue high-risk, high-reward ideas during their most creative years.

There are many complex reasons for the increased training periods, including an academic culture that emphasizes the need for longer, sometimes multiple, postdoc positions to build a stellar CV. There is a shortage of faculty vacancies, and institutions often insist that recruits win independent funding before appointing them to tenure-track posts. And there is too little emphasis on alternative scientific careers, such as industry, law, teaching and policy.

Many young researchers baulk at the prospect of such an extended period of limited intellectual autonomy. It is also a concern to veterans such as myself. I fear that science may be suffering because of a failure to encourage the independence of the next generation of great minds.

My own pathway to independence involved a three-year postdoctoral fellowship in human genetics in the lab of Sherman Weissman at Yale School of Medicine in New Haven, Connecticut. I was fortunate to be mentored by an adviser who encouraged autonomy and creativity. I used the opportunity to develop an innovative approach, called chromosome jumping, for crossing large strands of DNA to identify genes responsible for inherited disorders. It was a good launching pad; I received my first R01 grant from the NIH at age 34, the same year I began a faculty position at the University of Michigan in Ann Arbor.

In my lab at the NIH, I strive to cultivate the independence of young scientists as early as possible. One of my strategies is to assign new recruits a 'thinking period' devoted to formulating project ideas. Through an iterative process involving myself and the recruit, we refine the research direction until we have settled on a good fit. I think this strategy has worked well in encouraging forward thinking, but it may still be a halfway solution. For the most creative of young scientists, nothing can equal the chance to have a lab of one's own.

To provide such opportunities, several programmes aimed at promoting greater independence at earlier career stages have sprung up over the years, producing some spectacular investigators. And so, after much consultation with outside advisers, the NIH this week launched its own effort, the Early Independence Award Program (see http://go.nature.com/nFqYE5), which will initially support ten creative young scientists to pass almost immediately from completing a PhD to running their own laboratories. The awards will be paid by the NIH Director's Common Fund and administered through a peer-reviewed application process, supporting an investigator at a level of US$250,000 in direct costs per year for five years — the equivalent of a standard NIH R01 grant.

Unlike many similar programmes, the awards will give students flexibility to seek a position at any suitable institution. Applicants will need to work with the institution's academic leaders to negotiate an independent position that would be activated if they win an award. We hope that department heads will find this an attractive tool for recruiting talent to invigorate their institution's research environment. For its part, the institution must provide the young investigator with space and resources, and a level of mentoring equivalent to that provided to assistant professors.

I am aware that many speed bumps may lie on this expressway to independence. The programme requires highly motivated and mature applicants who are talented and confident enough to launch their own research programme and negotiate support from a department chair. And it requires institutions willing to support an award winner who will be unusually young in their career. The pilot programme, which we expect to be highly competitive, will issue its first awards next year. Although not intended to replace traditional postdoctoral training, the pilot can be scaled up if successful.

This programme is not for everyone, and postdoctoral positions will continue to expand the skills and experience of most young scientists. But for exceptional individuals with the intellectual and experimental sophistication to initiate an independent career at the end of doctoral training, this programme will provide the opportunity. I have been involved in the launch of many pilots, including that of the Human Genome Project, but I have a special affinity for this one: the future of biomedical research relies on the creativity and energy of its investigators. Unleashing that capability at all stages of a scientist's career should be a priority for us all.

Francis Collins is director of the US National Institutes of Health. e-mail: francis.collins@nih.gov

Garage bilogist

This reminds the old saying, that science can be absorbing interest to whoever with relentless curiosity and passions. Across Europe and US, a number of people are cropping up termed the so-called 'DIYbio'. They do biological experiments in their garage or kitchen or other places. They are not furnished with high-tech labs, but they run for their passions. Now they even begin to meet regularly to converse with each other. In a way, scientific activities should become common in people's daily life and not be exclusive to scientists. It is the spirit of inquiring into the Nature and liberating one's self from the ego. Unfortunately, normal education seems destroying rather than corroborating.

Nature, 467 :634 doi:10.1038/467634a

Amateur scientists who experiment at home should be welcomed by the professionals.

For the past two years, a group of molecular-biology enthusiasts has met regularly in Cambridge, Massachusetts, to discuss science. Their conservation is not entirely theoretical: they swap stories about the experiments they perform in rudimentary labs built in their kitchens, basements and garages. These meetings are not unique: similar gatherings are cropping up across the United States and Europe, as amateur scientists get together to compare protocols and results from experiments they design and conduct at home.

Do-it-yourself biologists emerged into the spotlight after the first meeting, in a Cambridge pub, in 2008. Their exploits have since earned them a moniker fit for the headlines of the twenty-first century: biohackers (see page 650). Media coverage has taken its toll on the public's perception of 'DIYbio'. Stories in the press are often peppered with sweeping claims of the monumental advances to be made by unleashing the talents of the public at large on important biological questions. Equally common are breathless warnings that a bioterrorist is busy crafting the next plague in a garage, safe from the watchful eye of the authorities.

Neither image rings true. Most biohackers are hobbyists who delight in crafting their own equipment and who tackle projects no more sophisticated than those found in an advanced high-school biology lab. This is not to belittle their achievements — the most basic lab experiments can be a challenge without the institutional infrastructure professional scientists take for granted. And it is not necessarily the sophistication of the techniques, but the questions to which they are applied, that makes for compelling science. Nevertheless, the high financial and educational barriers to cutting-edge molecular biology means that garage labs are unlikely to solve the world's energy or health problems any time soon. As for that imagined bioterrorist, US experts at the FBI's Weapons of Mass Destruction Directorate have investigated and found no sign of a biohacker who intends harm.

Nevertheless, the bureau is wise to plan ahead. The FBI has embarked on a laudable and proactive programme to establish ties with the amateur biology community. FBI agents attend DIYbio meetings and invite DIYbio leaders to conferences on bioterrorism. This has yielded some practical plans, such as notifying police and fire stations about local garage labs, to avoid unpleasant surprises or false alarms in the event of an emergency. But some in the biohacking community worry that the constant focus on bioterrorism has taken attention and resources away from a more pressing issue: basic biosafety. How should a biohacker dispose of unwanted genetically engineered bacteria? How does an amateur biologist avoid exposure to fumes from the chemicals used to isolate and manipulate DNA? What is a safe bacterium for a hobbyist to play with?

These are questions that crop up daily in a garage lab, and amateur biologists have struggled to find answers. Although institutions such as the US National Institutes of Health (NIH) and the Centers for Disease Control and Prevention have established biosafety guidelines, these are aimed at institutional biosafety officers with training in the field. Laden with jargon and focused on advanced work with dangerous chemicals and pathogens that hobbyists are unlikely to encounter, the guidelines are little help in the garage. Does this knowledge gap provide an opportunity for professional scientists to engage and support the DIYbio community? Some researchers argue it does, with professionals helping garage biologists craft safety guidelines and standards that could be understood by the enthusiast. Biohackers could also be brought onto biosafety committees at their local university or medical centre. These committees are required by the NIH to include at least one member who is not a professional scientist. Serving on a such committee would expose the hobbyist to the regulations and protocols that research institutions use to protect workers and the environment.

Biohackers are an example of the growing 'citizen science' movement, in which the public takes an active role in scientific experiments. Citizen science can help stimulate public support for science, and can introduce fresh ideas from novel disciplines. Science is a professional business but it would be a shame if the only interested knock on the hobbyists' doors came from those in law enforcement.

Wednesday, October 6, 2010

A Brief story of Feynman

On BBC radio Feynman was paid a tribute by Brian Cox, who is a particle physicist in Manchester University in UK.

Tuesday, October 5, 2010

Producing FFLO states

Nature, 467: 535–536:

Atomic gases cooled down to nanokelvin temperatures and confined in optical or magnetic traps have helped to realize and investigate fundamental many-body quantum phases of matter1, 2. An investigation by Liao et al.3 on page 567 of this issue now shows how such ultracold systems are also moving to centre stage in the quest for an exotic form of superconductivity — the elusive FFLO superconducting state of matter that was proposed more than 40 years ago by Fulde and Ferrell4 and Larkin and Ovchinnikov5.

In condensed-matter physics, an arbitrarily small attraction between fermions (particles with half-integer spin, such as electrons) of identical but opposing spin and momentum can lead to the formation of bound pairs that have bosonic character (bosons being particles with whole-integer spin). Under specific conditions, such pairs can undergo the phenomenon of Bose–Einstein condensation (BEC), transforming the many-body system into a 'giant matter wave' with spectacular frictionless-flow properties — a superconductor or superfluid is born. This remarkable outcome of pairing, first proposed by Bardeen, Cooper and Schrieffer (BCS), is considered to be the conventional way in which superconductivity emerges in a wide range of materials. In the world of atomic physics, the same pairing mechanism has been studied thoroughly in three dimensions with equal two-component gas mixtures of fermionic neutral atoms1, 2, each component comprising atoms with one of two spin states (up or down). But what happens to such a BCS superfluid state if the two fermionic spin states are not present in equal numbers in the system?

In a solid-state material, such a spin-imbalance condition can be created by applying a magnetic field to the system. In ultracold atomic gases, a simple initial difference in the number of spin-up and spin-down atoms will do the job. Intuitively, one might think that an increasing mismatch in the number of spin-up and spin-down particles would make it harder for the opposing spins to meet each other and pair up, thus hindering superconductivity. And this is indeed what happens in experiments. Put in more technical terms, the Fermi surfaces of the two system components will have different sizes, and this difference will hamper the formation of the pairs and the ensuing BCS superfluid state (the Fermi surface is the boundary in momentum space that separates unoccupied states from occupied ones).

Fulde and Ferrell4, as well as Larkin and Ovchinnikov5, proposed a clever solution that would still allow a superfluid state to exist under spin-imbalanced conditions. They suggested a paired state in which the pairs are not at rest but instead have a net momentum. This FFLO state can be viewed as a kind of microscale phase separation, containing alternating superfluid regions and normal, non-superfluid regions, in which the extra atoms of the spin species that are in excess squeeze in. Although searches for such an exotically paired FFLO state have been carried out exhaustively in condensed-matter systems, and more recently in ultracold atomic gases, unambiguous experimental evidence has remained elusive. In their study, Liao et al.3 take a major step towards creating an FFLO state using ultracold fermionic atoms.


Seeing the image obscured by painted glasses

This is an interesting innovation. Unfortunately, I cant access the original article !

A new laser technique can capture an image of an object obscured behind painted glass.

Sylvain Gigan and his team at ESPCI ParisTech in France have devised a method that traces the scattered path that photons take as they pass through an opaque white material. On one side of a glass slide covered in thick white paint, the researchers projected the image of a flower. They illuminated this set-up with a laser and took a photograph from the slide's other side. After calculating the light's zigzagging journey through the painted glass, they were able to reconstruct the flower image.

With improvements, the technique might one day be used in medical imaging to see through opaque biological tissue such as skin.

Nature Commun. doi:10.1038/ncomms1078 (2010)

This year's Nobel Prize

This year's Nobel Prize has been conferred on two Russian-born British scientists, who made breakthrough in making single-atom thick 2D materials, namely, graphene. This graphene has been under intensive studies since their discovery. Some interesting facts are as follows:
(1)2D;
(2)made of carbon atoms;
(3)consisting of both planar sigma bonds, each of which containing a localized pair of covalent electrons that found the mechanical strength, and out-of-plane pi-bonds, which are extended and occupied by mobile electrons;
(4)the pi-bands have two complete Dirac cones, due to negligible spin-orbit coupling and various symmetries: inversion symmetry, time-reversal symmetry and 6-fold rotation symmetry. In the vicinity of these cones, the physics are governed by 2D Dirac equations.
(5)because of (4), highly conductive;
(6)Quantum Hall effect and Quantum Spin Hall effect have been predicted (and the former has been observed) in this material;
Not limited by this listing, it is guaranteed that in the future more new physics shall be exploited, such as the curvature effects and optical properties.