Gene Silencing Therapies Could Have Harmful Side Effects, Research Suggests (Posted by Meekus)

ScienceDaily (Mar. 28, 2008) — A dramatic new study published in the most recent issue of Nature questions some of the mechanisms underlying a new class of drugs based on Nobel Prize-winning work designed to fight diseases ranging from macular degeneration to diabetes.

Dr. Jayakrishna Ambati, a University of Kentucky researcher and the paper's senior author, has for years been investigating gene silencing, a 1998 discovery that won a Nobel Prize in Physiology or Medicine in unusually quick fashion in 2006.

While the prize-winning discovery remains important, the findings made by Ambati's lab show the mechanisms behind it are not as scientists once believed. In fact, Ambati's work imparts the need for caution in current clinical trials using the technology, as it may have potentially harmful effects on subjects.

Gene Silencing Leads to New Class of Drugs

In short, researchers in 1998 discovered a class of double-stranded RNA (dsRNA) that possessed powerful gene-silencing capabilities, or the ability to "turn off" disease-causing genes in the body.

The technique of targeting these dsRNA for single genes was refined with synthetic molecules called small-interfering RNA (siRNA). siRNA were thought to have the capability to interfere with specific disease-causing genes and prevent them from being expressed.

Because gene-targeted silencing with siRNA does not involve permanent DNA mutations, this approach rapidly gained popularity throughout biomedical research. The breakthrough, with the powerful ability to turn off genes, has become a standard research tool for genetic studies and has resulted in a new class of 21st century drugs designed to silence disease-causing genes in the body or disarm an invading virus by knocking out its genes.

Many diseases including age-related macular degeneration, diabetes, kidney disease, cancer, Lou Gehrig's and Parkinson's have been heralded as candidates for siRNA therapy, creating a wave of on-going clinical trials.

New Discovery Shows Therapies Could Have Harmful Side Effects

Ambati, professor and vice chair of ophthalmology and visual sciences at the University of Kentucky College of Medicine, and his colleagues have made a critical discovery that challenges the view that siRNA's therapeutic effects are imparted solely through RNA interference.

Ambati and collaborators argue that siRNA functions generically rather than specifically, thus the new class of drugs being formulated may actually adversely affect blood vessel growth in a variety of organs.

"siRNAs are used in every area of biomedical research and are thought to be exquisitely specific in targeting a single gene," Ambati said. "My lab made the surprising discovery that siRNAs, including those in clinical trials, do not enter cells or trigger RNAi. Rather, we found that they generically, regardless of their sequence or target, bind a receptor known as TLR3 on cell surfaces and block blood vessel growth in the eye, skin and a variety of other organs."

Blocking blood vessel growth is beneficial in a variety of diseases. Prime examples include wet AMD, an eye disease hallmarked by the abnormal growth of blood vessels beneath the retina, as well as cancer. However, blocking blood vessel growth by administering siRNA intravenously could be detrimental if it impacts other organs, according to Ambati's study.

Ambati, however, quickly notes the Nobel Prize-winning discovery is still valid.

"RNA interference does, of course, exist," said Ambati, a University Research Professor and the Dr. E. Vernon Smith & Eloise C. Smith Endowed Chair in Macular Degeneration Research. "It is just that siRNA functions differently than commonly believed -- not via RNA interference."

Ambati said the main implications of his research are two fold:

1. for researchers to understand how siRNAs actually work
2. for clinical trials of siRNA to be approached with great caution.

Ambati's lab also showed that people with a mutation in the TLR3 receptor would be resistant to the generic effects of siRNAs, thereby providing hope for personalized medicine in this population.

The next steps, Ambati said, are to better understand the generic mechanism of siRNA that inhibits blood vessel growth and to discover how to render it useful in creating treatments for the many conditions that would benefit from such effects. His lab also will work to refine siRNAs to potentially achieve their promise of precise gene targeting.

UW study finds surprising genetic causes of schizophrenia / Seattle P-I, TOM PAULSON (Posted by Andy)

As if the science of how genetics leads to disease isn't already complex enough, researchers in Seattle and Long Island, N.Y., say individuals appear to develop schizophrenia from a varying smorgasbord of bad genes rather than common genetic flaws.

Scientists at the University of Washington and Cold Spring Harbor Laboratory report in Friday's edition of the magazine Science that multiple errors or deletions in a person's genetic code, or DNA, can lead to schizophrenia -- a psychiatric illness characterized by delusions and disordered thinking that today affects one of every 100 people.

The finding that multiple genes are involved is, by itself, not surprising, since other diseases or disorders are, or strongly appear to be, the result of many flaws rather than just a single bad gene. That fits nicely within the standard dogma of genetics.

What is surprising, challenging to the dogma and perhaps confusing to many experts who study the interplay between genetics and neuroscience, is that the UW-Cold Spring Harbor team found strong evidence that it's usually not the same set of genes going bad in people who develop schizophrenia.

"It's different genes in different people," said Dr. Jon "Jack" McClellan, a UW psychiatrist and a co-author of the report. This is a big challenge to the conventional wisdom, McClellan said, adding that he believes this could turn out to be the same for most other complex psychiatric diseases -- if not for all diseases that arise without a simple genetic flaw.

"The standard dogma is that any complex trait (such as mental illness) is going to be caused by the cumulative effect of multiple, common defects," said Dr. Mary-Claire King, a world-renowned geneticist and also one of the UW co-authors on the report.

"But that's not what we found."

It's long been clear, she said, that there had to be some sort of genetic contribution to this debilitating illness, since schizophrenia tends to run in families.

But the familial tendency still seemed kind of sporadic, King said, and there is the mystery of why such a self-defeating genetic disorder should exist at all. Considering the evolutionary process of natural selection, she said, schizophrenia genes should not persist because most of those who are afflicted tend to not produce children.

"The genes should have been selected out," King said. "There have been a lot of these paradoxes with schizophrenia."

King and McClellan worked with geneticist Jonathan Sebat and his Cold Spring Harbor colleague Shane McCarthy, along with the UW's Dr. Tom Walsh, Evan Eichler and others.

They employed some powerful, relatively new techniques of computerized genetic analysis to resolve these mysteries.

The goal was to examine the genome (an individual's entire genetic code, in humans more than 3 billion units of DNA) for patterns that might reveal some answers. The scientists examined the DNA of 150 people with schizophrenia (most of them patients at Western State Hospital) and compared what they found with the genetics of 268 people without the illness.

Assuming that the genes of most interest would be those involved in neural development and brain function, they looked for any differences. All individuals have some level of genetic errors or mutations in their genome. The researchers found that people with schizophrenia had flaws in brain-related genes 15 percent of the time compared with 5 percent in healthy people.

But it was never the same set of genes going bad.

"They were all different," King said. "The only way we could have found this was to look at the overall (genetic) profile."

While this certainly complicates the exploration of the genetics of schizophrenia, McClellan said it does reveal some common "neurological pathways" that may lead to better treatments for those with this mental illness. The many different malfunctioning genes in schizophrenics, he said, all play their parts within a limited number of brain-related functions.

Instead of chasing after individual genes to identify and develop new drugs for schizophrenia, McClellan said, this research suggests the focus should be on fixing the problems that arise -- owing to the widely varying genetic flaws -- on the biochemical pathways that govern brain development and function.

"This certainly shows why we should treat patients as individuals," he said. This shouldn't just be a marketing mantra followed by some generic, uniform therapeutic approach to illness, McClellan said, especially if -- as this study indicates -- individual variation occurs even at the most basic, genetic level of illness.

King said she recognizes that not everyone will be happy with, or even accept, the conclusions that they've drawn from this peculiar finding (even though the study was replicated by a team at the National Institutes of Health). It's not just about challenging dogma, she noted; it's also a challenge to a lot of established, funded studies already well under way.

"A lot of those approaches, based on the assumption that they are looking for common or shared genetic mutations, aren't going to work," King said.

Potential New Natural Plant Products For Use As Drugs, Herbicides Or Crop Protectants (Posted by Luke)

I thought this was relevant to our discussion of GMOs

"John Innes Centre scientists have found that plants may cluster the genes needed to make defence chemicals. Their findings may provide a way to discover new natural plant products of use as drugs, herbicides or crop protectants. Using a gene cluster that makes an antifungal compound in oats as a template, they uncovered a previously unknown gene cluster making a related compound in a very different species, and now want to extend the search to other plants.

Anne Osbourn and colleagues previously found that the genes needed to make an antifungal compound in oats, called avenacin, were next to each other in the genome. One of a group of chemicals known as triterpenes, avenacin is produced exclusively by oats and protects the roots against a wide spectrum of fungal diseases. Gene clusters are common in bacteria and fungi but extremely rare in plants. Maize has a gene cluster for a defence-related compound, and another possible cluster has been reported in rice.

Could other plant gene clusters exist, and how do they arise? To investigate this, the researchers used the 'signature' of the avenacin genes to scan the genome of the model plant Arabidopsis. Publishing in the journal Science, they identified a gene cluster for a new pathway that makes and modifies a triterpene called thalianol, which has not been found in plants before. The thalianol gene cluster consists of four genes next to each other in the Arabidopsis genome. The first gene, responsible for making thalianol, is from the same family as the gene for the first step of the avenacin pathway in oats. The next three genes in the thalianol cluster are responsible for making sequential modifications to thalianol. Having successfully discovered one gene cluster, the researchers now plan to look for other gene clusters that may produce novel natural products of value for crop protection or as medicines, and investigate how and why these clusters evolve.

Although the oat, maize, rice and this new Arabidopsis gene clusters make related products, they have been assembled independently of each other as a result of relatively recent evolutionary events. This suggests that plant species are able to show remarkable plasticity in their genomes to assemble these gene clusters. Understanding the evolutionary driving forces behind their assembly will give insights into why some plant product pathways are maintained in these clusters whilst others are not, and this may have implications for our understanding of plant metabolism.

Clustering genes together lets plants easily inherit an entire pathway. The thalianol gene cluster is one of the most conserved areas of the genome, suggesting that this beneficial combination of genes has recently and rapidly spread throughout the population. Breaking up a gene cluster can have severe consequences. When the avenacin pathway is blocked then unfinished intermediates accumulate that can have a toxic effect on the roots, making them deformed and ineffective. Intermediates which affect plant growth also accumulate when the thalianol synthesis pathway is blocked. If these intermediates accumulate in parts of the plant where the thalianol pathway is usually not present then they cause severe stunting of growth. Dr Ben Field, who contributed to the research, said "This suggests that gene clusters, as well as keeping beneficial combinations of genes together, may prevent toxic side-effects by strictly controlling where and when the pathway is switched on.""
Article adapted by Medical News Today from original press release.

Cloned Meat

As we have started to discuss Genetically Modified Food and its pros and cons, another thing to consider in comparison and contrast is cloned meat.

As we discussed, it is pretty easy to clone animals now (see diagram on the left), but some have also raised concerns as to whether such meat would be safe for human consumption. Think about it for yourself - given what you know so far about how GMOs and cloning differ in terms of their techniques and the extent to which the modify the genetics of an organism, what do you think?

The Daily Show has a very funny take on the issue. How is it that one calculates that one in four steaks isn't tasty? Wow, I guess science has all the answers...... click HERE to watch.

When to start HIV medication?

A new article about when it is best to start children on anti-HIV treatments - and so getting at the questions that came up earlier in the semester in terms of these medications.

Regulating Immortality - Stem Cell Control

A new paper this week details the complex regulatory mechanisms that play a part in keeping stem cells so versatile.

And one the the key players? It turns out to be something called a "microRNA" - yes, as we know, RNA does everything, so why shouldn't it also sometimes act as a transcription factor too?

The mechanisms of genetic regulation are only the much more complex the closer you look......

THE TOTIPOTENT ZEBRAFISH MAY SAVE BILLIONS OF BRILLIANT BLASTOCYSTS FROM DESTRUCTION

Zebrafish Enables Cell Regeneration Studies To Help Understand, Treat Human Disease

ScienceDaily (Mar. 19, 2008) — One aquarium fish’s uncanny ability to regenerate essentially any cell type has given scientists a way to mimic cell loss that occurs in diseases such as Parkinson’s and diabetes then watch how the fish make more of them.


“What we are pinning everything on is the idea that humans also have this capacity, but it’s sort of locked up,” says Dr. Jeff S. Mumm, biologist at the Medical College of Georgia.
Dr. Mumm, along with his partner in science and life, Dr. Meera Saxena, founded the company, Luminomics, Inc., to help fellow scientists unlock that capacity. “The forefront of medicine is not what humans are limited to, but what biology can do,” says Dr. Mumm. “This little fish is telling us what biology is capable of. With the same general set of genetic tools, these animals can do something we can’t: regenerate lost cells and tissues. Our job is to figure out which tools in which combination or sequence afford fish this capacity, then apply this knowledge toward the creation of regenerative therapies for humans.”
While working as a postdoctoral fellow at Washington University in St. Louis, Dr. Mumm used the resilient zebrafish to study retinal development. As a student at the University of Iowa, he studied the regeneration of olfactory receptor neurons, which enable the sense of smell. They are one of the few neuronal populations that regenerate throughout life in mammals: the usual human response to lost neurons is scarring and disease.
“If you have a cell type in your body that you lose, a lot of times, the end result is a particular degenerative disease state,” Dr. Mumm says. “So if you lose dopaminergic neurons in your brain, you end up with Parkinson’s. If you lose the insulin-producing cells of your pancreas, you begin to develop diabetes. There are literally hundreds of degenerative diseases. Still very little is known about how individual cell types are regenerated.” Scientists have tried to figure out how to re-grow whole organs or appendages. “What we wanted to go after was a much more clinically relevant disease model where we target a particular cell type that we know has ramifications for our health.”
Using targeted cancer therapy as a model, he developed a way to light up cells of interest, such as the insulin-producing cells of the pancreas; destroy them; then see what it takes for the lights to come back on. The same fluorescent protein that illuminates the cells links them to an enzyme, nitroreductase, which can kill them when a particular prodrug also is introduced.
This targeted destruction is called an inducible cellular ablation system, and Luminomics uses it to produce zebrafish models of degenerative disease that scientists can study. “If you know the cell type involved in a disease, we can use this system to model it. If we want to go after a particular muscular dystrophy, we express it in muscle. If we want to go after Parkinson’s, we express it in the dopaminergic neuron population.”
Scientists can watch cells die, see how their death affects the organ system, then remove the prodrug and study how cells repopulate.
Because the zebrafish’s genome is mapped and easily altered, scientists can also produce mutant fish that, like humans, no longer – at least spontaneously – regenerate this cell type. Information gained from watching the lights come back on in the inducible model provides clues on where to focus efforts to rekindle regeneration in the mutants.
“What the system we have developed does is provide us inroads to understanding the genetics and chemicals that can modify the genetics,” Dr. Mumm says. “There may be drugs out there that can help us find what we can do, not what we normally do.”
Most cells that are mature or differentiated into a specific type, such as a neuron or kidney cell, have, at least in the past, been considered unable to produce more cells like themselves. That ability was believed largely limited to stem cells. “The closer we look, cells with that kind of potential exist in more places than we ever thought. Even some differentiated cells appear to have the capacity to reproduce themselves and give rise to something new, one of the basic definitions of stem cells,” says Dr. Mumm.
Humans have much in common with zebrafish and most animals. “For the most part, we are all a piano with the same 88 keys. The PAX6 gene, for example, makes an eye in a fish, makes an eye in a drosophila, or fruit fly, and makes an eye in us. But the way those genes are combined in time and space creates many different tunes, and that is how many different body plans come out the other end,” says Dr. Mumm.
The tune of the nimble zebrafish body allows indeterminate growth capacity: put a full-grown zebrafish in a bigger tank with more food and it gets bigger. “The fish appear to have resident stem cells for every single tissue component of their bodies that they are able to regulate,” says Dr. Mumm.
Harvard researchers reported amazing evidence of their regenerating ability in 2002 in the journal Science when they showed that within two months of removing 20 percent of a zebrafish’s heart, it had grown back. A zebrafish with a specific genetic mutation grew scar tissue, a response more typical of what humans would do, assuming they survived.
Dr. Mumm has served as president and research director of Luminomics, Inc., since it was founded in 2004. Now that he and Dr. Saxena have relocated to Augusta, he’ll refocus on making new findings in cellular regeneration while Dr. Saxena directs the company. “I’ll probably be one of the biggest customers for the company,” he says.
“It actually plays well to our strengths,” Dr. Saxena says. She thrives on managing details while her husband prefers chasing new information. MCG’s incubator also seems a good fit. The two looked at many opportunities where he could continue basic science while she directed the company. One of Augusta’s many strengths was making the core laboratory facilities available to MCG scientists and incubator occupants alike. “As simple as an idea as it is and as obvious, it is rare,” says Dr. Mumm.

http://www.sciencedaily.com/releases/2008/03/080317155040.htm




zebrafish embryos




you MUST add these lil' guys to your aquarium!
wikipedia says: "Zebrafish are hardy fish and considered good for beginner aquarists [NICE!]. Their ease of keeping and breeding, beauty[oh la la], price and broad availability may all contribute to their popularity [as well as their totipotency!]. They thrive best at temperatures above 22 degrees Celsius and below 27 degrees Celsius. They feed on worms and small crustaceans and on insect larvae[gross!]. They also thrive as shoals of 6 or more, although they do interact well with other fish types in the Aquarium[the other fish are jealous because these guys can recreate their own organs and shit].

Genetic Music

Some Links to examples of gene sequences transposed into MIDI., prepared by Mary Anne Clark, Texas Wesleyan University.

artist/scientists using genome sequences as musical scores. For the most part, pitches are assigned to the four amino acid identities, and then other qualities such as timbre, duration, velocity etc are determined by molecular qualities of the acids, or the proteins they code such as molecular weight, molecular volume, biochemical category, protein folding pattern, hydrogen bonds, dissociation constants(?), water solubility etc.

Dr. Nobuo Munakata believes that audio representation of genome sequences are more accessible to the human brain than patterns of letters, and thus hopes that one day the sonification of genetic material will aid in the recognition of genes; that we will be able to, one day, draw connections between genetic sequences as we are able to connect "twinkle twinkle" to "abcdefg." He has posted a number of his projects on his site, in addition to links to more genetic musicians pages. Here is an example of his work:

or: link


When bacterial cells are exposed to sunlight, a lot of photoproducts accumulate in DNA, but they manage to replicate in the presence of damaged bases. Crucial genes in this mutagenic response were identified by Dr. Takeshi Kato in 1977 and later shown to be composed of an operon of two genes termed umuD and umuC. After N-terminal peptide of UmuD is cleaved off, the proteins make a complex and bind to damaged portion of DNA, aiding polymerase to circumvent the block. Sequences of messenger RNA, UmuD, and UmuC proteins are played successively

(statement)

Peter Gena, a sound department professor at SAIC has also done genetic compositions. They are more complicated than Munakata's, because they consider more molecular factors, that determine parameters like 'duration' which is absent in Munakata.

Mary Anne Clark's own compositiona are particularly interesting to me, especially "FOX-P2 (The "Human Language Gene")",(listen) because i felt like a gene like this would have been the obvious entry point for inquiries about the relationship between music and the human genome. I looked up FOX-P2 on Entrez Gene and one of the references it displayed was this:

FOXP1 and FOXP2 expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement.

(link)
A summary of evidence for this gene's expression shows that what scientists know about its nature, they know from the apparent consequences of its loss.


-dania

Obesity Study Sheds Light On How Genetics Affect Risk and Onset of Common Diseases (posted by Esther)

In a paper published in the journal Nature, a team of deCODE scientists detail a major mechanism through which genetic factors contribute to major public health problems. In its work on the inherited components of dozens of common diseases, deCODE has discovered gene variants that significantly affect individual susceptibility or protection against disease.

In the common forms of these conditions – such as obesity, type 2 diabetes and cardiovascular diseases – deCODE has previously shown that genetic variants confer increased or decreased risk by upregulating or downregulating the activity of major biological pathways. As a result, these variants place individuals on a spectrum of risk, with most of the population clustered at roughly average risk and a smaller number of people at either significantly higher or lower risk.

In the new paper, the deCODE team and collaborators from Merck demonstrate one of the principal ways in which the activity of biological pathways is functionally perturbed in a quintessentially complex condition: obesity. Through analysis of adipose tissue from some 1700 Icelandic participants in obesity research cohorts, the deCODE team showed in data derived from primary human tissue that variations in gene expression – in the up-regulation or downregulation of how genes are translated into proteins – have a major impact on several parameters of clinical obesity.

The deCODE team then used its unique resources for genome-wide linkage and association analysis to demonstrate that variability in gene expression, like overall risk for disease, has a significant inherited component that can be linked to specific versions of genetic markers.

“One of the observations we have made in our work on the isolation of disease genes is that the genetic risk of common diseases is often conferred by variations in the sequence of the genome that affect expression of genes. Hence, one of the ways to approach the study of common diseases is through the analysis of gene expression. This paper provides a substantial contribution towards the understanding of gene expression in man and one example of how it can be used to expand our knowledge of one disease, namely obesity,” said Kari Stefansson, CEO of deCODE.

The paper, “Genetics of gene expression and its effect on disease,” is published March 16 on Nature’s website, and will appear in a subsequent print edition of the journal.

http://www.sciencedaily.com/releases/2008/03/080318200625.htm

New Genes from Nowhere? - Transposons maybe aren't "Junk"

We haven't discussed this in class yet, so now seems like a good time - especially as we consider genetic modification and what seems to be questionable tinkering with genetic material from the outside. 

As it stands, though we know viruses sometimes insert their DNA into ours. Furthermore, some "jumping genes" - called "transposons" - within our genome move from one location to another not infrequently over evolutionary time. 

This article discusses how transposon "junk DNA" may have come to some use in fruit flies: re-purposed to actually be a functional gene. This adds yet another mechanism of mutation and means by which big genetic changes can evolve quickly.  Read more HERE

A related article and study in opossums (yes, opossums) shed more light on 1) how junk DNA can evolve functionality, and 2) how much of this has to do with evolving into regulatory genes!

Safer Gene Therapy May Be Possible

As we learn about the technique of Gene Therapy this week, we find a tchnology and approach with which promise but little recorded success. One major porblem has been the specificity with which the genes can be delivered to their intended target cells - aer all it is only usually in a subset of cells where a particular gene of interest is active. 

Reaserch this week is honing in on how to better tailor viruses as vehicles for gene therapy, and avoiding their hitting the wrong target - in this case, the liver.  The adenovirus shown above is the vector of study and they are finding it is through the hexon protein (see graphic) that this virus gains access to the liver - the thought now is how to disrupt that.   Full article is HERE

3 DEAD & A COW EGG, Genius or Mad Scientist? (posted by Lale)

Scepticism over cloning from dead

Dr Zavos' cloning work has evoked wide criticism

(taken from here)
A controversial scientist, who failed in his attempts to clone a human in January, has met further scepticism over his latest cloning claims.

US fertility doctor Panos Zavos says he has created a cloned embryo using tissue from dead people.

Experts said such actions would exploit the vulnerability of grieving people who had been bereaved.

And the Royal Society also questioned "a lack of evidence" behind Dr Zavos' claims.

It is grossly misleading to suggest that you can replicate a loved one. Professor Richard Gardner of the Royal Society

Dr Zavos told a press conference in London he had successfully combined genetic material from three dead people with cow eggs to make embryos that were an identical copy of the deceased.

He said he took DNA from blood samples from an 11-year-old girl who had died three days earlier in a car crash.

The other corpses whose tissue he took included an18-month-old toddler who had died following surgery, and a 33-year-old man.

Two of the three experiments were successful, creating embryos that Dr Zavos claimed would be "potentially viable" if left to grow in the human womb.

Dr Zavos said he had not done this yet and had stopped the embryos' development at an early stage when cells begin to divide and multiply rapidly.

But he said his current work was a major step forward, showing this could be a way to clone humans in the future.

He said similar studies had been carried out successfully in animals using dead tissue with good results.

He said the animal offspring produced had none of the deformities reported with other cloning methods.

Scepticism

Other scientists condemned Dr Zavos' actions.

Professor Richard Gardner, chair of the UK's Royal Society working group on stem cell research and cloning, said: "The work using human genetic material and cow eggs that Dr Zavos claims to have carried out would not be allowed under British law and is both scientifically questionable and ethically unacceptable.

"It is grossly misleading to suggest that you can replicate a loved one, such as a child lost in a road accident, by producing a cloned person with the same genetic material."

I'm not in the business of exploiting anyone Scientist Dr Panos Zavos

He said it was impossible to evaluate Dr Zavos' claims because his work had not been checked through proper scientific peer review.

Professor Gardner said: "Even more worrying is that Dr Zavos sees this work as a first step towards human reproductive cloning, which he still appears to want to carry out.

"The scientific community, and society as a whole, should be concerned about this because current evidence shows reproductive cloning is medically unsafe, scientifically unsound and socially unacceptable."

Dr Zavos denied suggestions that his work was unethical and exploited grieving parents.

He said all of the relatives involved knew they were taking part in research and there was no prospect at this stage of them getting new cloned babies.

"I'm not in the business of exploiting anyone. I have never done that. There are sensitivities here that we've dealt with in a professional manner."

He said the aim in the future would be "to replace the child and not to resurrect the child".

Dr Simon Fishel, managing director of the Centres for Assisted Reproduction (CARE) group of fertility clinics, said it was time for a worldwide ban on reproductive cloning.

"This would remove the false hope given by mavericks to patients."

He said using human DNA in a cow's egg would only create confusion rather than understanding of reproductive technology.

"At worst this is misleading and exploitative to the patients funding the research," he said.

ANOTHER ARTICLE ON SAME TOPIC IN "NEW SCIENTIST" HERE.