Decades-old artificial heart valves still going strong
Two video clips of two Starr-Edwards artificial valves can be seen in action in this week’s online issue of the New England Journal of Medicine. The video was taken by doctors at the Montreal Heart Institute in Quebec during a cardiac catheterization procedure of a 67-year old woman. What is amazing is the fact that these valves, which are working properly and in tip top shape, were implanted 38 years ago [1].
In another case study, a 74-year old man had a double valve replacement with Smeloff-Cutter aortic and Starr-Edwards mitral prostheses 40 years ago. No additional surgery except a pacemaker implantation has been required during the last 4 decades. The latest ECG showed the valves to be intact [2].
Other follow-up studies indicate that the Starr-Edwards valve “represents a standard that still needs to be achieved by newer prostheses.” [3]
This is the lasting legacy of the retired engineer Lowell Edwards who, together with the surgeon Albert Starr, developed the valves almost 50 years ago. The first valve was successfully implanted in 1960. Edwards then founded Edwards Lifesciences, which today remains as one of the world’s leading manufacturer of medical devices. According to Nature News,, over a quarter of a million people received Starr-Edwards artificial valves until last year when the company stopped their manufacturing in favour of newer models.
Lowell Edwards was awarded the American Medical Association’s Layman’s Citation for Distinguished Service in 1982, only the 6th person so far to receive the honor. The citation described the innovator as
“a man of honor and courage whose inventive genius brought about the development of the artificial heart valve and whose long devotion to human welfare in the science of medicine has given new life and hope to victims of heart disease throughout the world.”
References:
1. Piazza N, Gregoire J. Images in clinical medicines. Starr-Edwards heart valves. N Engl J Med. 2008 May 22;358(21):e24.
2. Gödje OL et al. Thirty-year results of Starr-Edwards prostheses in the aortic and mitral position. Ann Thorac Surg. 1997 Mar;63(3):613-9.
3. Suezawa T et al. Forty-year survival with Smeloff-Cutter and Starr-Edwards prostheses. Ann Thorac Surg. 2008 Mar;85(3):e14-6.
Stem cells in the most unexpected places
Time was when pleuripotent stem cells were supposedly only available from human embryos which led to heated debates on ethics and morality.
Since then, multipotent stem cells have been isolated from different organs of the human body, be it from the umbilical cord blood, the bone marrow, even from the skin. Recent research studies have now pinpointed even more unexpected sources of stem cells.
Stem cells in menstrual blood [1, 2]
Researchers at the University Pittsburgh’s McGowan Institute of Regenerative Medicine observed that menstrual blood stromal cells (MenSCs) exhibit a great capacity for self-renewal and multipotency.
Stem cells in breast milk [3]
On the other side of the globe, researchers at the University of Western Australia recovered the stem cell markers nestin from breast milk. These cells physically resemble stem cells and could potentially behave like stem cells.
If nestin and MenSCs indeed prove to be as plastic and pleuripotent as embryonic stem cells, then, we may have found stem cell sources which are unlimited, inexpensive, most of all, noncontroversial. Furthermore, these cells are easily collectable without resorting to invasive techniques.
Sources:
- Eureka Alert, 23 April 2008
- Patel et al. Cell Transplantation 2008; 17: 303-311
- Science Alert, 10 February 2008
Protecting the “dignity of creation” and its effects on Swiss scientific research
The constitution of a small mountain country requires “account to be taken of the dignity of creation when handling animals, plants and other organisms”. [1]
You`d think that such a constitution must be based on religions such as Buddhism which holds all living creatures sacrosanct from the single-celled to the high complex.
Actually, what is being referred to is the Swiss Federal Constitution. Based on this, the Gene Technology Law took effect in 2004 which stipulates that any scientific research should respect “the dignity of creation.” (German: Würde der Kreatur).
Animal activists were the first to agree that such a law is needed to protect the rights of animals, be it from toxicology studies to genetic manipulation. And rightly so. However, recent propsed addition to the Animal Protection Act actually requires everybody - not only scientists - but also farmers and pet owners to uphold the dignity of animals. Dog owners, for example, might be required to have a license, a document that may be granted only if they are proven to be capable of caring for their pets. Hamsters should only be kept in pairs and fish can only be killed under anesthetics.
But that`s not all. There is a new angle to this legislation that baffle both scientists and laymen alike. The “dignity of plants” has also been recently brought into the forefront which can drastically affect current as well as future plant research.
The main problem is how to define “plant dignity”, a term which is not clear to either plant biologists and funding agencies. The Federal Ethics Commitee on Non-Human Biotechnology (ECNH) gives the following concrete example:
“Terminator technology” is a genetic modification of plants so that a sown seed germinates normally, but the developing plant then produces seeds that are unable to germinate. What impacts does this technology have on agriculture? Does this affect the Würde der Kreatur in plants? And what precisely constitutes the dignity of a plant?” [1]
According to Nature News [2], ECNH
“… has created a decision tree presenting the different issues that need to be taken into account for each case. But it has come up with few concrete examples of what type of experiment might be considered an unacceptable insult to plant dignity. The committee does not consider that genetic engineering of plants automatically falls into this category, but its majority view holds that it would if the genetic modification caused plants to ‘lose their independence’ — for example by interfering with their capacity to reproduce. The statement has confused plant geneticists, who point out the contrast with traditional plant-hybridization technologies, for example in roses, which require male sterility, and the commercial development of seedless fruits.”
As a resident of Switzerland, I cannot help but wonder at the extremes and contrasts I have observed in this country. Respecting “dignity” of animals nonwithstanding, authorities granted the permission to shoot down a border-crossing brown bear earlier for human safety reasons, causing strong outcry in neighboring Italy.
Switzerland is home to 2 of the most innovative and highly respected research institutions in the world – European Organization for Nuclear Research- (CERN) in Geneva and ETH (Swiss Federal Institute of Technology) in Zurich. It is also the proud headquarters of two of the biggest pharmaceutical companies in the world – Roche and Novartis, both based in Basel. Yet, it has one of the most restrictive legislation on biotechnology research in Europe. While many European countries, including Germany are slowly easing up restrictions on stem cell research, Switzerland is moving in the opposite direction.
How the new legislation will affect research in Switzerland, only time will tell. Currently, Switzerland is home to many of the world`s talented scientists. Among many Europeans, most especially Germany, Switzerland is a highly desirable destination because it offers good research facilities, high pay, low taxes, and overall good quality of life. However, if such legislations make life difficult for these scientists, an exodus of of talent out of this country cannot be ruled.
Sources:
[1] Dignity of creation, ECNH
[2] Nature News 23 April 2008
The Acquisitions Continue: Roche buys Piramed
Roche is increasing its stakes in biotechnology research by buying 100% of Piramed, a UK-based biotech company. This small, privately-owned company is the rising star on developing therapies targeting P13 kinase (P13-K) pathway which plays “an important role in disease progression and in resistance to chemotherapeutics in cancer cells.” [1]
With the acquisition, Roche also acquires Piramed`s two major P13-K projects on oncology and inflammatory medicine. This solidifies the collaboration between Piramed and Genentech (partly owned by Roche) on these research programs.
This is not the first time that big pharma takes over small but promising biotech firms. Pfizer bought Angiosyn in 2005. Merck acquired Sirna in 2006. Sanofi Aventis joined forces with Regeneron last year.
According to analysts [2], such mergers and acquitions are not necessary favorable in the long run. Small companies are saved from financial troubles at the expense of the larger firms which tend to suffer from slow growth and postmerger integration problems – problems which can divert cash from R&D and further slow down the pipeline.
References:
1. Roche Media News, 15 April 2005
2. Danzon et al. Mergers and acquisitions in the pharmaceutical and biotech industries. NBER Working Paper No. 10536, May 2004
The year that was: major events in 2007
Nature`s Daniel Cressey listed several events as among the most newsworthy in 2007. Some of these events are discussed below.
Biotechnology
November was a good month for biotechnology. American and Japanese researchers derived pleuripotent stem cells from human skin. American researchers also finally succeeded cloning primate embryos in the same month. Both events are major breakthroughs in stem cell research.
This year, two big names in genomics - James Watson and Craig Venter – had their full genome sequenced. In the meantime, American start ups are offering personalized genetic information service (see October post).
Climate Change
The Intergovernmental Panel on Climate Change (IPCC) was co-winner of the Nobel Prize for Peace. In the meantime, the Northwest Passage that connects Atlantic and Pacific Oceans was practical ice-free and passable – a record low in the arctic ice cover. If the IPCC reports and this ice shrinkage do not convince people of the reality of global change, nothing ever will.
Pharmaceutical scandals
China’s former head of food and drug regulatory agency was executed in July after having been convicted of corruption. In the USA, the Avandia scandal rages on. The USA FDA required an additional black box warning for the diabetes medication Avandia (rosiglitazone) labelling last year but Avandia`s troubles didn’t stop there. The latest involved a US senate inquiry and a leak by an NEJM reviewer.
Safety issues
The July earthquake in Japan caused a leak in a major nuclear reactor, reawakening concerns over nuclear energy safety in general.
Two incidences of major biosecurity lapses were reported this year. In the UK, a leaky pipe caused an outbreak of foot-and-mouth disease. In a bioweapons research lab at the Texas A&M University, researchers were exposed to biohazards.
Space technology
Japan and China launched moon probes in 2007 though there were doubts whether China’s claims of success were authentic. China also tested a space weapon by shooting at one of its defunct satellites, scattering potentially dangerous debris in space.
Wired magazine considered the following as the top 10 scientific breakthrough of 2007:
10. Transistors Get Way Smaller
9. Scientists Clone Rhesus Monkey to Produce Stem Cells
8. Planet Discovered That Could Harbor Life
7. Engineers Create Transparent Material as Strong as Steel
6. Soft Tissue from T. Rex Leg Bone Analyzed
5. Laboratory Mice Cured of Rett Syndrome
4. Enzymes Convert Any Blood Type to O
3. Mummified Dinosaur Excavated and Scanned
2. Chimpanzees Make Spears for Hunting
1. Researchers Turn Skin Cells to Stem Cells
References:
Cressey D. News 2007. Nature 450, 1134-1135 (2007)
Rowe A. Top 10 Scientific Breakthroughs of 2007. Wired 27 Dec 2007.
The First Rapid Blood Test for MRSA is in the Market
In recent years, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection have been on the rise. This has especially become a problem in hospitals where MRSA infections have become synonymous to healthcare-associated infections.
S. aureus is a very common bacterial species that causes pimples and mild skin and wound infections. However, years of antibiotic use gave rise to strains which are resistant to the antibiotic methicillin as well as to other drugs. The MRSA strains can cause life-threatening conditions such as sepsis, infections of surgical sites, and pneumonia.
The US FDA has recently approved the first quick test to identify MRSA in the blood. Using molecular methods, the BD GeneOhm StaphSR Assay can detect genetic material from the common, less dangerous methicillin-sensitive S. aureus (MSSA) as well as the drug-resistant deadly MRSA strains [1, 2]
Early detection of MRSA infections is crucial in their treatment and management. Using standard diagnostic laboratory tests, it takes 2 days to identify MRSA in blood samples. With the new rapid test, results are available within 2 hours. This is especially good news to the public health community which had to deal with the rapid rise in the incidence of MRSA infections in hospitals and clinics. Immunocompromised patients are especially susceptible.
The BD GeneOhm StaphSR test is manufactured by BD Diagnostics, a subsidiary of BD of Franklin Lakes, N.J.
[1] FDA News, 2 Jan 2008. FDA Clears First Quick Test For Drug-Resistant Staph Infections.
Symposium on antiviral applications of RNAi
The European Science Foundation (ESF) and the European Molecular Biology Organization (EMBO) are organizing a symposium on “Antiviral Applications of RNA Interference” on 5 to 10 April 2008.
The symposium will take place in Sant Feliu de Guixols, Spain, located 120 km north of Barcelona.
RNA interference (RNAi) is a promising new technology with a great potential for use as an antiviral tool. The approach allows specific inhibition of gene expression either through the degradation of specific RNA molecules or hindering of transcription of certain genes. The first clinical trials to evaluate the efficacy and safety RNAi technologies have recently been started.
The symposium will mainly focus on human pathogenic viruses and “will be the first comprehensive meeting combining RNAi and antiviral research.”
“The meeting will cover the most recent progress in the field by 22 invited presentations of internationally renowned researchers, complemented by shorter contributed oral presentations of young scientists and by poster presentations.”
Nonclinical Studies: The Latest in Adult Stem Cell Research in Mice
In the latest issues of Nature and Science, two articles report on promising therapies using adult stem cells.
American and German researchers demonstrated that embryonic stem cells can mend post-infarction heart muscles without causing ventricular tachyarrhythmias. Following cardiomyocyte implantation, mice were protected against the induction of ventricular tachycardia. This was not evident when adult and bone marrow stem cells were used in the engraftment. The reason may be the fact that embryonic heart stem cells have a high degree of expression of the gap-junction protein connexin 43. Bone marrow stem cells engineered to express this protein afforded similar protection [1].
In another in vivo study, researchers successfully treated sickle-cell anemic mice using adult murine stem cell lines. The test mice were genetically-engineered to have a sickle-cell hemoglobin allelle, producing a “humanized sickle cell anemia mouse model.” The adult stem cells from these animals were reprogrammed to become pluripotent and their faulty allele was corrected by gene-specific targeting. Following transplantation of these reprogrammed and corrected cells, treated mice exhibited higher RBC counts and hemoglobin levels than control mice [2].
The results of these studies demonstrate potential cell-based therapies using adult stem cells.
[1] Roell, W. et al. Nature 450, 819-824 (6 December 2007)
[2] Hanna, J. et al. Science doi:10.1126/science.1152092 (6 December 2007)
Sanofi-Aventis Joins Forces with Regeneron
The French pharmaceutical giant Sanofi-aventis is joining the biotech bandwagon. Initially thought to be a slowmover in the biotech field, it is now stepping up its drug development program and is particularly concentrating on the development of therapeutic antibodies.
In order to attain these goals, Sanofi-aventis has decided to increase its stake in the biotech company Regeneron from 4% to 19%. As part of the payment, Sanofi-aventis will fund a big part of research costs in the next five years. Research will focus on the development of fully human monoclonal antibodies [1, 2].
Part of the colloboration portfolio are two promising drugs, namely:
- Antibody to Interleukin-6 receptor (IL-6R), indicated for rheumatoid arthritis, currently undergoing Phase I clinical trials.
- Antibody to Delta-like ligand-4 (Dll4), indicated for tumors, to enter clinical development in 2008.
From this collaboration, Sanofi-aventis aims to develop about 20 drug candidates annually and targets about 30 new drug submissions by the end of 2010 [1,2].
[1] 29 Nov 2007, Sanofi-aventis press release
[2] 29 Nov 2007, Regeneron press release
Conference on Functional Genomics and Disease
The 3rd Conference on Functional Genomics and Disease will be held in Innsbruck, Austria next autumn. On 1 to 4 October 2008, over 50 speakers will present papers and conduct workshops on the topics ranging from molecular biology to epigenetics to personalized medicine. Of particular interest are the cutting-edge applications of genomics and proteomics in the field of cancer research (oncogenomics), neurology (neurogenomics), and vascular medicine (angiogenomics). Other topics of medical significance are lipidogenomics, inflammatory diseases and ageing. The conference is sponsored by the European Science Foundation. The first two conferences were held in Prague in 2003 and Oslo in 2005.
More details are to be found at: