Sunday, August 1, 2010

Therapeutic Cloning

Therapeutic Cloning
The word cloning rings in frightening images of duplicate human beings created of the a person. When 'Dolly the sheep' was cloned in an experiment, it was subject to a lot of public outrage. The process used here was Adult DNA cloning, which is different from therapeutic cloning. In therapeutic cloning there is no sperm fertilization or uterus implantation involved. Thus, a new human being is not created, but rather an organ, a nerve tissue or skin is produced. To help people understand this process better, few therapeutic cloning facts are discussed below.

Therapeutic Cloning Facts

What is Therapeutic Cloning?
Therapeutic cloning is a method through which stem cells are created, but used only for repairing damaged tissues in the parent clone cell. These stem cells can be used to grow alternate varieties of organs such as heart, liver and kidney, which can be transplanted as an exact match. This method can create stem cells which could produce sound nerve cells for patients suffering from Parkinson's or Alzheimer's disease.

The person in search of healthy stem cells will have to offer a non-sperm and non-egg cell, from which the DNA would be taken out. This DNA will contain two replicates of each human chromosome. It will then be introduced into a donor egg, which would have its DNA and nucleus already removed. This process is known as somatic cell nuclear transfer. The newly inserted egg would now behave like it has just been fertilized, and would start to divide to form an embryo. It is from this embryo that stem cells would be taken out and refined to generate the required healthy tissue. Read more in detail on embryonic stem cell research.

Therapeutic Cloning Benefits
In case of successful embryo creation through therapeutic cloning, replacement organs can be produced and a lot of people who are suffering from this condition can be cured. Numerous lives can be saved and people can live longer as well. Several benefits with regards to this include:

* As the organ's DNA exactly matches with the person's, the fear of rejection while transplant vanishes.
* The practice of waiting for a donor to obtain the desired organ would come to a halt as the required organ can be generated at will.
* Unlike an already used organ from a donor, the new one would be brand new and without any problems which could have come with the a used organ.
* Kidney transplants will become easier as the need of a donor who would have to shorten his lifespan will erase.
* There is a possibility that therapeutic cloning can find cures for diseases which cannot be treated otherwise.
* Lives of patients in want of an organ donor will be saved.

Problems With Therapeutic Cloning
It is true that there are tremendous benefits of therapeutic cloning. This however, does not in any way dilute the various hurdles the process has to face before rendering successful. Few therapeutic cloning problems and obstacles are discussed below:

* Research on therapeutic cloning over years has been promising, but adult cells by nature do not have a wide scope of application. Stem cells from embryos have proven to have greater flexibility than adult cells.
* Through the somatic cell nuclear transfer, a new person comes to existence. When stem cells are removed from the embryo, it is killed and many people consider this as murder. Pro-life supporters are therefore in protest of therapeutic cloning.
* There are still a few defects in the process, as a few tests have shown people and animals to develop diseases or tumors post therapeutic cloning. These shortcomings need to be eliminated before approval.
* The major concern regarding therapeutic cloning is, where to get eggs from? To start this process at a wide level, millions of eggs would be needed. Removing eggs from women is painful for them and not practically feasible as well. Thus, efficient ways to produce stem cells need to be discovered before taking therapeutic cloning to the next level.

Human Cloning

Human Cloning

Cloning an organism involves replicating the DNA of that organism in a new organism that, as a result, has the same exact features and characteristics. Human Cloning would mean recreating the person that is being cloned. With the successful cloning of Dolly The Sheep, Human Cloning, long the staple of science fiction, is on the verge of becoming a reality.

How would Human Cloning work?
Human Cloning, if it is ever done, will be carried out by the same method that brought forth Dolly, Reproductive Cloning.

In Reproductive Cloning, the nucleus is removed from a body cell of the organism to be cloned and this nucleus is inserted into an enucleated egg, that is, an egg whose nucleus has previously been removed.

The egg with the new nucleus is then treated to electric or chemical treatment to simulate cell division. The resulting embryo is transferred to a host uterus to develop properly and eventually be given birth to.

The new-born organism will be a replica of the original organism, but not the exact same actually, since it will have DNA derived from both the organism as well as the egg.

Why would Human Cloning be done?
Cloning animals, especially endangered species, is one way of preserving the species from dying out entirely. But why would anyone want to clone human beings? There are enough of us already on the planet without resources enough for the well-being of all of us. So why bother to clone?

Well, one reason is pure scientific research. We've already come a long way. After Dolly, scientists have managed to clone various animals. So cloning humans seems the next logical step and a very important one it would be too.

Cloning humans could also prove a major breakthrough as far as cloning for therapeutic purposes is concerned. Cloning could be used to produce new organs for organ transplants. Since the cloned organ, produced from a body cell of the person needing the transplant, would have the same genetic code, there would be less risk of the body rejecting the new, transplanted organ. Cloning could also be used to treat Cancer, Alzheimer's and Parkinson's Diseases, and host of other illnesses.

Cloning would allow infertile couples to have their own genetic offspring or otherwise normal couples to order designer babies. It could also be used to bring back to life your dead ancestors. So if you want to give birth to your great-great-grandmother, you can. Just as long you managed to preserve some samples of her body cells.

One American couple reportedly is willing to pay $500,000 to clone their dead infant daughter.

And then there are some who would like to clone themselves and thereby achieve eternal life.

Is it ethical to go ahead and clone humans?
Well, sometimes one of a kind is more than one can tolerate. But, on the serious side, many of the leading Scientists involved in cloning research, like Ian Wilmut and Richard Gardner, have expressed serious doubts and ethical dilemmas over the cloning of human beings.

Firstly, reproductive cloning is not yet a fool-proof method. It took 272 attempts before Dolly was produced. This means 272 embryos either failed to develop properly or were discarded as defective. In other cases, if the embryos weren't miscarried, a large percentage of the animals born showed a high degree of abnormality and died quickly or had to be euthanized. Those successfully cloned have showed many health problems and none have lived to a ripe old age so far.

Now, since human beings consider themselves a class apart, obviously many moral problems would arise with treating defective human embryos or new-born, handicapped babies in the very same manner.

There is also no way of predicting what the intelligence level and capabilities of a human clone would be. What would be the psychological and societal implications for it as an individual? What kind of a life or future would it have? Since we don't know, many people consider it unethical to go ahead and clone.

But that argument doesn't hold much water with others. After all, we have no way of knowing exactly what sort of a person a normally conceived embryo will turn out to be either.

Is Human Cloning legally allowed?
Reproductive Cloning of Humans is banned is many countries around the world, including the USA and the UK, and allowed in some. Therapeutic Cloning is allowed to some degree, but there is already a clamor against it from religious and pro-life organizations, many of whom are more acquainted with its theological implications than its theoretical possibilities.

Scientists Post Lower Speed Limit for Cell-Signaling Protein Assembly

Scientists Post Lower Speed Limit for Cell-Signaling Protein Assembly

The apparently random self-assembly of molecular threads into the proteins that make the body work is far less frantic than previously thought, Michigan State University scientists say. That discovery could be a key to help unlock the nature of some diseases.

How proteins spontaneously "fold" from wiggling chains of amino acids into a wide variety of functional -- or malfunctioning -- three-dimensional molecules is one of the biggest mysteries in biochemistry.

"People thought they understood how protein diffusion worked, but now our data suggests they're wrong by a factor of 1,000," MSU physics and astronomy assistant professor Lisa Lapidus said. "Now we can start changing the models -- we've been trying to solve protein folding for 50 years, and now we're advancing our fundamental understanding of what unfolded proteins do before they fold."

The findings were published online by the science journal Proceedings of the National Academy of Sciences. Lapidus was joined in the research by University of Zurich Institute of Physical Chemistry researcher Steven Waldauer, whose recent MSU doctoral dissertation formed the basis of the study, and University of California, Davis, scientist Olgica Bakajin.

Proteins, which do most of the work in the body's cells, are chain molecules composed of amino acids. The order in which the amino acids are assembled was charted by the Human Genome Project, but the function of the protein depends on its shape, and how a protein folds is not yet understood. Much of the process is random and diffusive, like sugar moving through an unstirred cup of coffee.

Most proteins can fold in milliseconds, although there are so many possible combinations that left to chance it's physically impossible, scientists agree. So they speculate that there must be built-in folding pathways -- but those remain unproved. Now physics is helping make sense of biology, posting a lower speed limit for proteins as they spontaneously assemble into their lowest-energy, so-called natural state -- like a relaxed spring.

"In order to measure how quickly this random, unfolded state changes confirmations, we had to design an entirely new apparatus as well as design and fabricate a microfluidic chip capable of observing proteins within a fraction of a millisecond after being allowed to refold," Waldauer explained. Two lasers were employed to observe the formation of the immunoglobulin proteins.

"We found that the nature of the unfolded state is far from intuitive and that a protein will change from one random conformation to another much more slowly than previously thought," he said.

Scientists know that errors can occur in folding, and these are associated with a variety of diseases including Alzheimer's, ALS, cystic fibrosis and diabetes. Lapidus and colleagues speculate that the rate of the process could influence the outcome. Proteins that wiggle more rapidly, for example, may be more prone to sticking together and causing plaques such as those in Alzheimer's. The team's discovery may lead to new therapeutic strategies for this class of diseases.

"I believe this measurement of intramolecular diffusion is something that will be crucial for any subsequent studies of protein folding or mis-folding," Lapidus said.

RNA Offers a Safer Way to Reprogram Cells

RNA Offers a Safer Way to Reprogram Cells

In recent years, scientists have shown that they can reprogram human skin cells to an immature state that allows the cells to become any type of cell. This ability, known as pluripotency, holds the promise of treating diseases such as diabetes and Parkinson's disease by transforming the patients' own cells into replacements for the nonfunctioning tissue.

However, the techniques now used to transform cells pose some serious safety hazards. To deliver the genes necessary to reprogram cells to a pluripotent state, scientists use viruses carrying DNA, which then becomes integrated into the cell's own DNA. But this so-called DNA-based reprogramming carries the risk of disrupting the cell's genome and leading it to become cancerous.

Now, for the first time, MIT researchers have shown that they can deliver those same reprogramming genes using RNA, the genetic material that normally ferries instructions from DNA to the cell's protein-making machinery. This method could prove much safer than DNA-based reprogramming, say the researchers, Associate Professor of Electrical and Biological Engineering Mehmet Fatih Yanik and electrical engineering graduate student Matthew Angel.

Yanik and Angel describe the method, also the subject of Angel's master's thesis, in the July 23 issue of the journal PLoS ONE.

However, the researchers say they cannot yet claim to have reprogrammed the cells into a pluripotent state. To prove that, they would need to grow the cells in the lab for a longer period of time and study their ability to develop into other cell types -- a process now underway in their lab. Their key achievement is demonstrating that the genes necessary for reprogramming can be delivered with RNA.

"Before this, nobody had a way to transfect cells multiple times with protein-encoding RNA," says Yanik. (Transfection is the process of introducing DNA or RNA into a cell without using viruses to deliver them.)

In 2006, researchers at Kyoto University showed they could reprogram mouse skin cells into a pluripotent, embryonic-like state with just four genes. More recently, other scientists have achieved the same result in human cells by delivering the proteins encoded by those genes directly into mature cells, but that process is more expensive, inefficient and time-consuming than reprogramming with DNA.

Yanik and Angel decided to pursue a new alternative by transfecting cells with messenger RNA (mRNA), a short-lived molecule that carries genetic instructions copied from DNA.

However, they found that RNA transfection poses a significant challenge: When added to mature human skin cells, mRNA provokes an immune response meant to defend against viruses made of RNA. Repeated exposure to long strands of RNA leads cells to undergo cell suicide, sacrificing themselves to help prevent the rest of the body from being infected.

Yanik and Angel knew that some RNA viruses, including hepatitis C, can successfully suppress that defensive response. After reviewing studies of hepatitis C's evasive mechanisms, they did experiments showing they could shut off the response by delivering short interfering RNA (siRNA) that blocks production of several proteins key to the response.

Once the defense mechanism is shut off, mRNA carrying the genes for cell reprogramming can be safely delivered. The researchers showed that they could induce cells to produce the reprogramming proteins for more than a week, by delivering siRNA and mRNA every other day.

Key Step in Body's Ability to Make Red Blood Cells Discovered

Key Step in Body's Ability to Make Red Blood Cells Discovered

Researchers at UT Southwestern Medical Center have uncovered a key step in the creation of new red blood cells in an animal study.

They found that a tiny fragment of ribonucleic acid (RNA), a chemical cousin of DNA, prompts stem cells to mature into red blood cells. The researchers also created an artificial RNA inhibitor to block this process.

Such interventions, if fruitful in humans, might be useful against some cancers and other diseases, such as polycythemia vera, in which the body produces a life-threatening excess of blood cells. Conversely, a drug that boosts red blood cell production might be useful against anemia, blood loss or altitude sickness.

"The important finding is that this microRNA, miR-451, is a powerful natural regulator of red blood cell production," said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and senior author of the study, which appears in the Aug. 1 issue of Genes & Development.

"We also showed that a man-made miR-451 inhibitor can reduce miR-451 levels in a mouse and block blood-cell production. We hope that this inhibitor and similarly functioning molecules might lead to new drugs against the fatal disease polycythemia vera, which currently has no therapies," said Dr. Olson, who directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic and Clinical Research in Pediatric Oncology.

Red blood cells, which carry oxygen throughout the body, are created in bone marrow from stem cells. The body steps up its production of red blood cells in response to stresses such as anemia, blood loss or low oxygen, but overproduction of the cells increases the risk of stroke and blood clots.

RNA molecules, found throughout cells, perform several jobs. MicroRNAs often bind to and disable other types of RNA, preventing them from carrying out their functions.

Dr. Olson and his colleagues study many different types of microRNAs to determine their functions and to find therapeutic uses of artificial microRNAs.

"miR-451 is found in great abundance in mature red blood cells, but its function was not known," said lead author David Patrick, a graduate student in molecular biology.

In the new study, the scientists created genetically engineered mice that could not make miR-451. The mice had a lowered red blood cell count and also had difficulty creating more red blood cells under conditions that usually stimulate production.

miR-451 works by interacting with another RNA involved in producing a protein called 14-3-3-zeta, which plays a role in the maturation of many types of cells, the researchers found.

The team also treated blood stem cells with an artificial RNA designed to inhibit miR-451. As a result, the number of red blood cells decreased.

Dr. Olson and his colleagues are pursuing a patent on miR-451 inhibitors and studying whether a microRNA-based drug might be useful in treating several blood-related disorders.

Other UT Southwestern researchers involved in the study were Dr. Cheng Zhang, assistant professor of physiology and developmental biology; Xiaoxia Qi, research scientist in molecular biology; and Dr. Lily Jun-Shen Huang, assistant professor of cell biology. Researchers from Texas A&M Health Science Center, Houston; Texas Heart Institute, Houston; and the University of Houston also participated.

Vascular-Targeted Photodynamic Therapy for Localized Prostate Cancer

Vascular-Targeted Photodynamic Therapy for Localized Prostate Cancer

NYU Langone Medical Center has begun a clinical trial offering vascular-targeted photodynamic therapy to patients with localized prostate cancer. This novel, minimally invasive procedure uses a light-activated drug to deliver light energy waves by way of laser fibers in order to destroy prostate cancer cells.

"This minimally invasive technique for localized prostate cancer offers the potential to destroy the cancer without making any incision or causing any potentially devastating sexual, urinary or reproductive side-effects," said Samir S. Taneja, MD, The James M. Neissa and Janet Riha Neissa Associate Professor of Urologic Oncology and director of the Division of Urologic Oncology at NYU Langone Medical Center and principal investigator for the national, multi-center clinical trial testing this technology. "This procedure only treats the cancerous part of the prostate gland, similar to how a lumpectomy might be done for breast cancer.

Photodynamic therapy is just one of the many personalized treatment options offered by the Smilow Comprehensive Prostate Cancer Center at NYU Langone Medical Center. The Center offers a wide range of the latest treatment options for prostate cancer including: open or robotic prostatectomy surgery, brachytherapy, external beam radiation therapy, cryotherapy and high-intensity focused ultrasound (HIFU), a focal therapy that uses high-energy sound waves to treat prostate cancer, now also in clinical trials at the medical center.

This Phase I/II photodynamic therapy trial is open to men diagnosed with localized prostate cancer -- determined by a needle biopsy and advanced imaging techniques -- who have chosen active surveillance, also known as "watchful-waiting. During the procedure, laser fibers are positioned over the prostate where cancer cells have been identified. Once in place, a photosensitizing drug called WST11 is administered to the patient intravenously and circulates throughout the blood stream for ten-minutes. The laser fibers are then activated to deliver a specific wavelength of light to the prostate for twenty-minutes. When the light comes into contact with the drug in circulation, the laser fibers destroy the blood vessels around the tumor shutting down the blood supply to the cancer. Patients are followed for a year after treatment with PSA tests after each visit and an MRI and needle biopsy performed at six months.

"Focal treatment of prostate cancer with techniques such as photodynamic therapy is an emerging paradigm since the over treatment of prostate cancer is a major concern for both physicians and patients," said Dr. Taneja who is also a member of the NYU Cancer Institute.

Recent European studies show photodynamic therapy successfully treats localized prostate cancer with minimal side effects. This study will investigate optimal dosage of the photosensitive drug and light-energy waves and measure outcomes of patients as well as long-term cancer control. Researchers believe the technology has the potential to treat any early stage prostate cancer as well as tumors in other organs of the body.

Cell-of-Origin for Human Prostate Cancer Identified for First Time

Cell-of-Origin for Human Prostate Cancer Identified for First Time

scientists have identified for the first time a cell-of-origin for human prostate cancer, a discovery that could result in better predictive and diagnostics tools and the development of new and more effective targeted treatments for the disease.

The researchers, from UCLA's Jonsson Comprehensive Cancer Center, proved that basal cells found in benign prostate tissue could become human prostate cancer in mice with suppressed immune systems, a finding that bucks conventional wisdom. It had been widely believed that luminal cells found in the prostate were the culprits behind prostate cancer because the resulting malignancies closely resembled luminal cells, said Dr. Owen Witte, a Jonsson Cancer Center member and director of the UCLA Broad Stem Cell Research Center.

"Certainly the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells," said Witte, senior author of the study and a Howard Hughes Medical Institute Investigator. "But we were able to start with a basal cell and induce human prostate cancer and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy."

The study appears July 30, 2010 in the peer-reviewed journal Science.

The researchers took healthy tissue from prostate biopsies and separated the cells based on their surface marker expression into groups of luminal cells and groups of basal cells. Using viral vectors as vehicles, they then expressed altered genes known to cause cancer into both cell populations and placed the cells in mice to see which developed cancer, said Andrew Goldstein, a UCLA graduate student and first author of the study.

"Because of the widespread belief that luminal cells were the root of human prostate cancer, it would have been those cells examined and targeted to treat the disease," said Goldstein. "This study tells us that basal cells play an important role in the prostate cancer development process and should be an additional focus of targeted therapies."

In normal prostate tissue, basal cells have a more stem cell-like function, Goldstein said, meaning they proliferate more to re-grow human prostate tissue. Luminal cells don't proliferate as much, but rather produce major proteins that are important for reproduction. Something is going awry in the basal cells that results in cancer and Witte and Goldstein plan to study those cells to uncover the mechanisms that result in malignancy.

Currently, there is a dearth of knowledge about how prostate cancer develops to treat it effectively in a targeted way, as Herceptin targets an out-of-control production of growth factor receptors in breast cancer cells. The major targeted therapy used for prostate cancer is directed at the androgen receptor and it is not always effective, Witte said.

The new human-in-mouse model system developed in the study -- created by taking healthy human prostate tissue that will induce cancer once it is placed in mice instead of taking malignant tissue that is already cancerous and implanting it -- can now be used to evaluate the effectiveness of new types of therapeutics. By using defined genetic events to activate specific signaling pathways, researchers can more easily compare therapeutic efficacy. The new model, by deconstructing tissue and then reconstructing it, also will aid in analyzing how the cells change during cancer progression.

"There are very few examples of taking benign cells and turning them into cancer experimentally," Goldstein said. "We usually study cancer cell lines created from malignant tumors. This study resulted in the creation of a novel model system that is highly adaptable, such that we can test any cellular pathway and its interactions with other genes known to induce cancer, and we can start with any type of cell as long as it can be reproducibly purified."

In this system, Witte and Goldstein know the "history" of the cells that became cancer, unlike the cancer cells lines used in other work.

"We know those cells are malignant, but we don't know how they got there," Goldstein said. "By starting with healthy cells and turning them into cancer, we can study the cancer development process. If we understand where the cancer comes from, we may be able to develop better predictive and diagnostic tools. If we had better predictive tools, we could look earlier in the process of cancer development and find markers that are better than the current PSA test at catching disease early, when it is more treatable."

Rising PSA levels can indicate the presence of cancer that is already developing in the prostate. However, now that it is known that basal cells are one root of human prostate cancers, scientists can study pre-malignant basal cells and uncover what they express that the healthy ones don't, perhaps revealing a new marker for early detection, Goldstein said. Also, a therapy directed at the pre-malignant basal cells about to become malignant could provide a way to prevent the cancer before it becomes dangerous.