Many women drink alcohol whether it is beer, wine, or liquor and this consumption can increase the risk for developing breast caner. In 2002, the Collaborative Group on Hormonal Factors in Breast Cancer published a report clearly showing a link between alcohol consumption and increased risk of developing breast cancer. In this study, scientists reviewed data from over 153,000 women (over 58,000 women with breast cancer and 95,000 women without breast cancer) who participated in 53 different studies conducted worldwide. Of the several questions explored in this analysis, one focus was to evaluate what contribution alcohol consumption made to altering the risk of developing breast cancer. The overall conclusion was that alcohol consumption raises the risk of developing breast cancer by 7% when those that drink alcohol were compared with those who don’t.
Breast cancer isn’t just one disease. There are multiple forms that it can take: ductal carcinoma, lobular carcinoma, hormone sensitive (estrogen and progesterone receptor positive), hormone insensitive. Ductal and lobular carcinoma arise in different locations -- either in the ducts within the breast (hence ductal) or within the milk producing glands (lobular). Hormone sensitivity means that there is expression of the estrogen receptor and the cancer is responsive to hormones (estrogen and progesterone) or it doesn’t express the receptors and therefore doesn’t respond to hormones. Ductal carcinoma is the most common form (70% of all breast cancers), with lobular carcinoma accounting for 30% of the cases. In the 2002 study, the analysis was between alcohol consumption and the risk of developing any form of breast cancer.
This week, an interesting new article looked at alcohol and breast cancer risk in a new light. Investigators from the Fred Hutchinson Cancer Institute in Seattle explored if alcohol consumption alters the type of breast cancer and focused on whether drinking alcohol contributes to the development of a particular form of breast cancer or if it is more general, affecting multiple forms of cancer. Interestingly, this analysis demonstrated that alcohol consumption raised the risk of developing lobular carcinoma but did not alter the risk of developing ductal carcinoma. In fact, the researchers found that alcohol affected hormone sensitive (estrogen receptor positive) lobular cancer formation.
What does this mean? It shows that different subtypes of cancer respond differently. They develop as a result of different causes and are influenced by different factors. Specifically, alcohol affects the development of lobular but not ductal cancer and uses estrogen in that process. How this happens is still unclear, but these findings are quite intriguing. These findings will help to understand how lobular cancers form and how estrogen affects them. It could lead to new methods to detect these cancers and maybe to how to prevent them in the first place.
Monday, August 30, 2010
Friday, August 20, 2010
non-coding and microRNAs
You mentioned the intricacies of the genome. I have heard the the term non-coding RNA. How does that fit into the scheme of the genome?
Thank you for the topic suggestion!
In the 1990s a new player took the stage in scientific research, microRNAs. This new player has changed the focus of how genes are regulated in the cell.
Previously, the major players in the cell were proteins. They are the functional unit and workers in the cell. For example, the protein called BRCA1 (breast cancer 1 protein) is involved in DNA repair when the DNA is damaged. It is also mutated in some people and that mutation is linked to the development of some forms of breast cancer.
Proteins are made by translation of a RNA molecule, remains in the cell for a defined period of time (depending on the specific protein) and is degraded by other protein-dependent mechanisms of various sorts. The RNA in the cell functioned to translate the code from DNA to the protein. Some specialized RNAs, messenger RNA, transfer RNA and ribosomal RNA, exist to help in this process.
That was prior to the 1990s and the recognition of non-coding RNAs, especially microRNA (aka miRNAs). Non-coding RNAs are RNA molecules that have a role in the cell, but do not create proteins to carry out that function. This includes the RNAs mentioned above (transfer, messenger and ribosomal) and also includes a newly identified class of RNAs that have very important roles in the cell, the small non-coding RNAs. This class now contains microRNAs, small interfering RNAs, and Piwi-associated RNAs. For today, the focus will be microRNAs.
MicroRNAs are short stretches of RNA nucleotides (the A,C,U,G bases) that are only 20-30 bases in length. It’s short (transfer RNAs, messenger RNAs can be 100-1000s of nucleotides long)! These miRNA are very important for controlling protein expression levels and do so by controlling the translation step from messenger RNA to protein. (For example, the BRCA1 gene is encoded in the DNA on Chromosome 17. When it is expressed the DNA is transcribed and a BRCA1 messenger RNA is created. This messenger RNA is then translated by transfer and ribosomal RNA and other proteins into the actual BRCA1 protein).
MicroRNAs control protein expression in a variety of ways - they bind to the messenger RNA and degrade it so there is no RNA template available to create the protein - or they bind to the messenger RNA and prevent the message from being translated into the protein by disrupting the translation machinery without altering the messenger RNA amount itself. In either case, the overall amount of the protein product is reduced and this can have dramatic consequences on the cell.
The real advantage of microRNAs is speed. They can rapidly control the level of protein in a cell, much faster than if a protein has to be made from turning on the transcription of the DNA, then creating the messenger RNA, then creating the protein. Alternatively, it can rapidly remove a protein from a cell by binding to the messenger RNA and essentially silencing it. Need more protein? Remove the microRNA bound to the messenger RNA and more protein will be translated! Have too much and need to eliminate protein quickly? Bind a microRNA to the messenger RNA and prevent protein translation.
This area of research has exploded! Since they were discovered, over 400 different microRNAs have been identified. They control expression of many proteins and are critically important in the cell. Many microRNAs have been shown to be altered in cancers (either too much or too little) suggesting that a problem (and therefore a potential therapeutic target) could be that microRNA expression is out of whack.
This discovery will change how scientists think about control of protein expression. Control of protein expression is no longer a linear process.
Just entering microRNA into the PubMed scientific literature search engine yields almost 8500 papers on the topic already! I think in the future we’ll see use of microRNAs and these other small non-coding RNAs as therapy to treat disease.
Thank you for the topic suggestion!
In the 1990s a new player took the stage in scientific research, microRNAs. This new player has changed the focus of how genes are regulated in the cell.
Previously, the major players in the cell were proteins. They are the functional unit and workers in the cell. For example, the protein called BRCA1 (breast cancer 1 protein) is involved in DNA repair when the DNA is damaged. It is also mutated in some people and that mutation is linked to the development of some forms of breast cancer.
Proteins are made by translation of a RNA molecule, remains in the cell for a defined period of time (depending on the specific protein) and is degraded by other protein-dependent mechanisms of various sorts. The RNA in the cell functioned to translate the code from DNA to the protein. Some specialized RNAs, messenger RNA, transfer RNA and ribosomal RNA, exist to help in this process.
That was prior to the 1990s and the recognition of non-coding RNAs, especially microRNA (aka miRNAs). Non-coding RNAs are RNA molecules that have a role in the cell, but do not create proteins to carry out that function. This includes the RNAs mentioned above (transfer, messenger and ribosomal) and also includes a newly identified class of RNAs that have very important roles in the cell, the small non-coding RNAs. This class now contains microRNAs, small interfering RNAs, and Piwi-associated RNAs. For today, the focus will be microRNAs.
MicroRNAs are short stretches of RNA nucleotides (the A,C,U,G bases) that are only 20-30 bases in length. It’s short (transfer RNAs, messenger RNAs can be 100-1000s of nucleotides long)! These miRNA are very important for controlling protein expression levels and do so by controlling the translation step from messenger RNA to protein. (For example, the BRCA1 gene is encoded in the DNA on Chromosome 17. When it is expressed the DNA is transcribed and a BRCA1 messenger RNA is created. This messenger RNA is then translated by transfer and ribosomal RNA and other proteins into the actual BRCA1 protein).
MicroRNAs control protein expression in a variety of ways - they bind to the messenger RNA and degrade it so there is no RNA template available to create the protein - or they bind to the messenger RNA and prevent the message from being translated into the protein by disrupting the translation machinery without altering the messenger RNA amount itself. In either case, the overall amount of the protein product is reduced and this can have dramatic consequences on the cell.
The real advantage of microRNAs is speed. They can rapidly control the level of protein in a cell, much faster than if a protein has to be made from turning on the transcription of the DNA, then creating the messenger RNA, then creating the protein. Alternatively, it can rapidly remove a protein from a cell by binding to the messenger RNA and essentially silencing it. Need more protein? Remove the microRNA bound to the messenger RNA and more protein will be translated! Have too much and need to eliminate protein quickly? Bind a microRNA to the messenger RNA and prevent protein translation.
This area of research has exploded! Since they were discovered, over 400 different microRNAs have been identified. They control expression of many proteins and are critically important in the cell. Many microRNAs have been shown to be altered in cancers (either too much or too little) suggesting that a problem (and therefore a potential therapeutic target) could be that microRNA expression is out of whack.
This discovery will change how scientists think about control of protein expression. Control of protein expression is no longer a linear process.
Just entering microRNA into the PubMed scientific literature search engine yields almost 8500 papers on the topic already! I think in the future we’ll see use of microRNAs and these other small non-coding RNAs as therapy to treat disease.
Thursday, August 12, 2010
Direct to Consumer genetic testing
There has been a lot of news lately about the accuracy and reliability of direct to consumer (DTC) genetic testing kits. These are relatively inexpensive testing kits that use a sample of your DNA, obtained by scraping the inside of your cheek, to analyze for gene alterations and to determine your genetic predisposition for a disease or other trait like hair color or if you smell that strange smell that asparagus turns your pee! Basically, you send your DNA sample to a company and they tell you your “risk” of developing different diseases over your lifetime. The issue is that these tests are not very reliable. Unfortunately, while the kits themselves are cheap, the profiling can be quite pricey. So, you are paying for data that may be worthless.
A few months ago, the FDA tested these kits. They bought 10 kits from 4 companies and sent 2 samples from each person. One sample had factual data about age, race and gender but the second sample had fictional data supplied to test the accuracy of the findings.
The results of the test were surprising. First, some of the companies failed to disclose before the test was submitted that the African American or Asian samples could not be accurately analyzed. Secondly, the different samples yielded different results. Some samples did not align with current medical conditions, i.e. existence of heart disease. One sample scored below average using one kit for risk of prostate cancer and hypertension but above average on a different kit for the same disease. Why are they different? They should be the same.
These results raise important scientific questions about genetic testing and personalized medicine. Several genes that predict how a patient will respond to a certain therapy have been identified. For example, estrogen receptor alpha and progesterone receptor alpha expression for administration of tamoxifen in breast cancer, expression of certain mutations of BRCA1 or 2 increases the risk for developing breast cancer, expression of K-Ras in colon cancer identifying those likely to respond to cetuximab or panitumumab, expression of EGFR protein predicts use of Iressa, gefitinib or erltinib as a lung cancer therapy. The list goes on. Personalized medicine and the genes known to help predict disease or response to therapy is powerful stuff. It can, and will, really change how patients are tested and treated for disease. It is a young field and changing rapidly as more is being understood, but it isn’t ready for companies like these that provide information on your risk for diseases. The data they provide is incomplete or worse, inconclusive and wrong. The data isn’t reviewed by a healthcare provider and therefore has no medical oversight. Providing such services just muddies the water and prevents real progress in understanding the science of diseases.
There is active debate about regulating these companies with some proposing a complete ban on them for now. Whatever happens, I just hope that this doesn’t keep people from believing in science and the power of the new technologies and insights being realized today.
A few months ago, the FDA tested these kits. They bought 10 kits from 4 companies and sent 2 samples from each person. One sample had factual data about age, race and gender but the second sample had fictional data supplied to test the accuracy of the findings.
The results of the test were surprising. First, some of the companies failed to disclose before the test was submitted that the African American or Asian samples could not be accurately analyzed. Secondly, the different samples yielded different results. Some samples did not align with current medical conditions, i.e. existence of heart disease. One sample scored below average using one kit for risk of prostate cancer and hypertension but above average on a different kit for the same disease. Why are they different? They should be the same.
These results raise important scientific questions about genetic testing and personalized medicine. Several genes that predict how a patient will respond to a certain therapy have been identified. For example, estrogen receptor alpha and progesterone receptor alpha expression for administration of tamoxifen in breast cancer, expression of certain mutations of BRCA1 or 2 increases the risk for developing breast cancer, expression of K-Ras in colon cancer identifying those likely to respond to cetuximab or panitumumab, expression of EGFR protein predicts use of Iressa, gefitinib or erltinib as a lung cancer therapy. The list goes on. Personalized medicine and the genes known to help predict disease or response to therapy is powerful stuff. It can, and will, really change how patients are tested and treated for disease. It is a young field and changing rapidly as more is being understood, but it isn’t ready for companies like these that provide information on your risk for diseases. The data they provide is incomplete or worse, inconclusive and wrong. The data isn’t reviewed by a healthcare provider and therefore has no medical oversight. Providing such services just muddies the water and prevents real progress in understanding the science of diseases.
There is active debate about regulating these companies with some proposing a complete ban on them for now. Whatever happens, I just hope that this doesn’t keep people from believing in science and the power of the new technologies and insights being realized today.
Friday, August 6, 2010
genes, pseudogenes and the increasing complexity of the genome
Research into the human genome has led us to understand that our DNA is very complex. The genes that make us who we are are encoded in our DNA. That is straightforward, right? The research that has taken place since the genome was sequenced 10 years ago has redefined what a gene really is.
In order to have a functional product from the DNA, the gene is transcribed from DNA into messenger RNA (mRNA) and then translated into a protein, the functional element in the cell. The simple (old) definition is that a gene is a made up of several parts, a coding region that holds the sequence for the protein that will carry out the function of that gene, a promoter region that controls how the gene is turned on and off and is usually found just in front of the coding region, and a third region called the 3’ untranslated region (3‘UTR) that controls how long the RNA will exist in the cell. There may be other control elements that determine if or regulate how a gene is expressed including enhancer regions that “enhance” the transcription of the gene in to RNA, but in essence, what constitutes a gene was easily defined. There was “extra” DNA that didn’t encode a gene, however, and this extra sequence was essentially useless. It didn’t have a role and was garbage or filler. It is unimportant.
Now, after 10 years of genomic research, some of the complexity of a gene has been realized. The “unimportant” sections of DNA, in turns out, are important. The definition of a gene isn’t so simple. Besides genes that code for proteins, there are pseudogenes that are the same sequence as genes but work to prevent the activity of the gene. Some genes, depending on where the sequence for them starts and stops, can produce many different proteins that have vastly different functions. These are called alternative stop codons (aka sites) and they can produce longer or shorter genes and lead to dramatically different functions!
Together all this means that there is more regulation of genes than previously thought! Our cells, and bodies for that matter, are extraordinarily complex. Each system has been finely and precisely coordinated to control how it works. This also means that there are new avenues that can be exploited for therapy. Now that new entities have been identified, novel and innovative ways to prevent or increase their function is being investigated. This could lead to a new therapy and hopefully will reduce unwanted side effects.
In order to have a functional product from the DNA, the gene is transcribed from DNA into messenger RNA (mRNA) and then translated into a protein, the functional element in the cell. The simple (old) definition is that a gene is a made up of several parts, a coding region that holds the sequence for the protein that will carry out the function of that gene, a promoter region that controls how the gene is turned on and off and is usually found just in front of the coding region, and a third region called the 3’ untranslated region (3‘UTR) that controls how long the RNA will exist in the cell. There may be other control elements that determine if or regulate how a gene is expressed including enhancer regions that “enhance” the transcription of the gene in to RNA, but in essence, what constitutes a gene was easily defined. There was “extra” DNA that didn’t encode a gene, however, and this extra sequence was essentially useless. It didn’t have a role and was garbage or filler. It is unimportant.
Now, after 10 years of genomic research, some of the complexity of a gene has been realized. The “unimportant” sections of DNA, in turns out, are important. The definition of a gene isn’t so simple. Besides genes that code for proteins, there are pseudogenes that are the same sequence as genes but work to prevent the activity of the gene. Some genes, depending on where the sequence for them starts and stops, can produce many different proteins that have vastly different functions. These are called alternative stop codons (aka sites) and they can produce longer or shorter genes and lead to dramatically different functions!
Together all this means that there is more regulation of genes than previously thought! Our cells, and bodies for that matter, are extraordinarily complex. Each system has been finely and precisely coordinated to control how it works. This also means that there are new avenues that can be exploited for therapy. Now that new entities have been identified, novel and innovative ways to prevent or increase their function is being investigated. This could lead to a new therapy and hopefully will reduce unwanted side effects.
Sunday, August 1, 2010
stem cells as cancer therapy?
One last stem cell related blog and I promise, I’ll move on to a new topic.
There have been some interesting articles in the science literature about the potential use of stem cells to treat cancer. This is based on basic research and is not yet used in any clinical trials or ready for prime time. It is an interesting idea that MAY show promise as a therapy someday but is NOT there yet. Therefore, I am not advocating that it should be sought out as a therapy now or that if this does exist anywhere it will be beneficial. Time will tell as more research is conducted if it is a good therapy or if some other therapy will come of out of this research.
Mesenchymal stem cells are cells found in the bone marrow. Actually, there are two types of bone morrow derived stem cells, hematopoetic (that go on to become white blood cells) and mesenchymal (that can differentiate into many cell types and are involved in wound/tissue repair). It also turns out that mesenchymal stem cells (MSC), because of their role in wound repair and tissue regeneration, migrate to cancer tumor sites. The current understanding is that tumor cells release agents called chemokines that attract MSCs to the site. The role of these MSCs within tumors is still largely unclear but it is thought that they may contribute to supporting tumor growth. Interestingly, scientists have been looking at how to use this migration capacity of MSCs to turn these cells into cells that deliver some form of therapy (aka a vector for cancer therapy). Basically, MSCs can be engineered to express a gene that will kill the tumor cells. For example, MSCs can be made to express the interferon beta protein and then used to target to melanoma tumors. Interferon beta has been shown to inhibit tumor growth by causing cells to stop growing and die.
The advantage of using MSCs instead of just injecting a drug or ingesting a pill is that MSCs could be better at targeting to a tumor site and reducing the unintended side effects by affecting non-tumor cells. This would be especially beneficial for tumors that are hard to access such a solid tumors in the breast, etc...
As I said at the beginning of this piece, this is a test of a theory that is being investigated. It is a very attractive idea, to use cells that preferentially go to tumor sites as a method to deliver therapy. There is still a lot that isn’t known yet, like will the MSCs themselves promote tumor growth? For now, it is a novel way to deliver therapy directly to the tumor site. Hopefully, this research will continue to progress.
There have been some interesting articles in the science literature about the potential use of stem cells to treat cancer. This is based on basic research and is not yet used in any clinical trials or ready for prime time. It is an interesting idea that MAY show promise as a therapy someday but is NOT there yet. Therefore, I am not advocating that it should be sought out as a therapy now or that if this does exist anywhere it will be beneficial. Time will tell as more research is conducted if it is a good therapy or if some other therapy will come of out of this research.
Mesenchymal stem cells are cells found in the bone marrow. Actually, there are two types of bone morrow derived stem cells, hematopoetic (that go on to become white blood cells) and mesenchymal (that can differentiate into many cell types and are involved in wound/tissue repair). It also turns out that mesenchymal stem cells (MSC), because of their role in wound repair and tissue regeneration, migrate to cancer tumor sites. The current understanding is that tumor cells release agents called chemokines that attract MSCs to the site. The role of these MSCs within tumors is still largely unclear but it is thought that they may contribute to supporting tumor growth. Interestingly, scientists have been looking at how to use this migration capacity of MSCs to turn these cells into cells that deliver some form of therapy (aka a vector for cancer therapy). Basically, MSCs can be engineered to express a gene that will kill the tumor cells. For example, MSCs can be made to express the interferon beta protein and then used to target to melanoma tumors. Interferon beta has been shown to inhibit tumor growth by causing cells to stop growing and die.
The advantage of using MSCs instead of just injecting a drug or ingesting a pill is that MSCs could be better at targeting to a tumor site and reducing the unintended side effects by affecting non-tumor cells. This would be especially beneficial for tumors that are hard to access such a solid tumors in the breast, etc...
As I said at the beginning of this piece, this is a test of a theory that is being investigated. It is a very attractive idea, to use cells that preferentially go to tumor sites as a method to deliver therapy. There is still a lot that isn’t known yet, like will the MSCs themselves promote tumor growth? For now, it is a novel way to deliver therapy directly to the tumor site. Hopefully, this research will continue to progress.
Monday, July 26, 2010
Science funding
I’ve been getting a few questions lately asking why isn’t this type of research (insert area of interest here) funded or why isn’t there a cure for (insert common disease here)? Well, in all honesty, these questions actually come up all the time, but recently they have resurfaced. Scientists are funded (fat and happy) and pharmaceuticals are expensive, so why isn’t there a cure for x or why isn’t there more focus on y? In reality, funding for science is far below what the general public perceives. Many interesting topics aren’t researched because scientists don’t have the funds to do so. It isn’t a lack of interest or that scientists are “hiding the cure” to make money, it is that there is less and less funding available.
Science is very expensive. Institutions including colleges, universities, pharmaceutical companies, provide most of the equipment for research, usually in core facilities so that there is general access. These machines are very specialized and very expensive, both to buy and to maintain. A majority of scientists rely on grant money to cover the cost of their staff, the supplies, and to a great extent themselves. As the economy has slipped, funding for science has also dried up. The National Institutes of Health (NIH) is the major sponsor of biomedical research and isn’t able to fund the same percentage of applicants it has in the past. This is for two main reasons. First, more scientists are applying and second, less money is allocated. Because of this, more scientists have relied on non-profit organizations that grant money for research. This is an excellent source of funding, but also limited. So, as funding has been cut, more people apply to non-profit groups, making that funding also much more competitive. And so on down the line. Pharmaceutical companies spend a lot of money on research and development. The number of drugs that are investigates far exceeds the slim number that make it to market. The further down the road of testing a drug that the drug fails and has to be removed from consideration, the greater the loss for the pharmaceutical company. If a drug looks promising but fails to do what is intended during phase II clinical trials, billions have been lost. Pharmaceutical companies do have a lot to gain from a profitable drug, but developing drugs is not a trivial venture.
Research takes time. Progress is made every day, but it may not be the type of progress that hits the headlines or astounds the general public. Research is just that - re-search. Experiments have to be repeated and confirmed prior to publishing. It is critical that findings are reproducible so that researchers are lead down the wrong path and bad decisions are made.
In a perfect world, there would be unlimited funds for research and cures for all things would exist. However, scientists are limited by the funding and resources they have. This is why it is important to keep funding research either through the NIH or through non-profit sources.
Science is very expensive. Institutions including colleges, universities, pharmaceutical companies, provide most of the equipment for research, usually in core facilities so that there is general access. These machines are very specialized and very expensive, both to buy and to maintain. A majority of scientists rely on grant money to cover the cost of their staff, the supplies, and to a great extent themselves. As the economy has slipped, funding for science has also dried up. The National Institutes of Health (NIH) is the major sponsor of biomedical research and isn’t able to fund the same percentage of applicants it has in the past. This is for two main reasons. First, more scientists are applying and second, less money is allocated. Because of this, more scientists have relied on non-profit organizations that grant money for research. This is an excellent source of funding, but also limited. So, as funding has been cut, more people apply to non-profit groups, making that funding also much more competitive. And so on down the line. Pharmaceutical companies spend a lot of money on research and development. The number of drugs that are investigates far exceeds the slim number that make it to market. The further down the road of testing a drug that the drug fails and has to be removed from consideration, the greater the loss for the pharmaceutical company. If a drug looks promising but fails to do what is intended during phase II clinical trials, billions have been lost. Pharmaceutical companies do have a lot to gain from a profitable drug, but developing drugs is not a trivial venture.
Research takes time. Progress is made every day, but it may not be the type of progress that hits the headlines or astounds the general public. Research is just that - re-search. Experiments have to be repeated and confirmed prior to publishing. It is critical that findings are reproducible so that researchers are lead down the wrong path and bad decisions are made.
In a perfect world, there would be unlimited funds for research and cures for all things would exist. However, scientists are limited by the funding and resources they have. This is why it is important to keep funding research either through the NIH or through non-profit sources.
Thursday, July 15, 2010
stem cells?!
Thank you to the submitter of this week’s topic: in light of my last blog, what about stem cells and why all the controversy? This is a fascinating topic and parts are hotly debated. Stem cells come in a several flavors. There are adult stem cells, hematopoetic (white cells in the blood) stem cells, embryonic stem cells (ES) and the most recently identified inducible pluripotent stem cells (iPS). These iPS cells are artificially derived cells that are created from adult cells by forcing the expression of a particular set of genes.
A common characteristic of all stem cells is that they are all slow growing cells that are “immature”. Given the appropriate signals, they can be coerced to develop into any cell in the body. The most easily manipulated are the embryonic stem cells, but these are highly controversial since they come from embryos (usually from ones that are donated after in vitro fertilization techniques. They are the frozen embryos that are not implanted or used in that process). Use of ES cells opens the whole debate about when life begins and it is morally right to use embryos in this manner, even if their fate would be to be frozen permanently? That is a discussion for another day.
The overall goal with stem cells is to isolate them from various sources, including by the way from fat cells in our bodies (I’d donate!), and stimulate them to become whatever cell type is necessary. Have a bad heart? Take stem cells and stimulate them to become heart cells that can be introduced into the ailing heart and “cure” it. In reality, this isn’t close to happening. Stem cells are being studied and understood more and more each day. The field has moved forward quite rapidly and hopefully will be widely used in clinical settings some day. For now, it is too soon to really use them in meaningful clinical ways, especially iPS cells. As more is understood about how these cells grow and (more importantly) how they don’t keep growing, the better their use will be as therapy. Until then, they are being used in cell culture models to understand more about how cells work and develop. A useful and informative by-product to these studies is that this information can be used by non-stem cell researchers to understand how those cells work as well. In other words, the research isn’t limited to just stem cells alone.
A common characteristic of all stem cells is that they are all slow growing cells that are “immature”. Given the appropriate signals, they can be coerced to develop into any cell in the body. The most easily manipulated are the embryonic stem cells, but these are highly controversial since they come from embryos (usually from ones that are donated after in vitro fertilization techniques. They are the frozen embryos that are not implanted or used in that process). Use of ES cells opens the whole debate about when life begins and it is morally right to use embryos in this manner, even if their fate would be to be frozen permanently? That is a discussion for another day.
The overall goal with stem cells is to isolate them from various sources, including by the way from fat cells in our bodies (I’d donate!), and stimulate them to become whatever cell type is necessary. Have a bad heart? Take stem cells and stimulate them to become heart cells that can be introduced into the ailing heart and “cure” it. In reality, this isn’t close to happening. Stem cells are being studied and understood more and more each day. The field has moved forward quite rapidly and hopefully will be widely used in clinical settings some day. For now, it is too soon to really use them in meaningful clinical ways, especially iPS cells. As more is understood about how these cells grow and (more importantly) how they don’t keep growing, the better their use will be as therapy. Until then, they are being used in cell culture models to understand more about how cells work and develop. A useful and informative by-product to these studies is that this information can be used by non-stem cell researchers to understand how those cells work as well. In other words, the research isn’t limited to just stem cells alone.
Tuesday, July 6, 2010
Using cells in tissue culture
The last blog about the HeLa cells made me think about a question that is asked all the time. If we have cells that can grow in culture and can be used to test all aspects of biomedical science, why do we need to test in animals and in humans? The short answer is that cell culture (or tissue culture) -- other terms for growing human or animal cells in plastic dishes in the lab -- is just one part of the whole puzzle. It is just one of the items in the toolbox. Ideas and theories about how cells work and how a drug may be beneficial to stop cancer growth or make a heart cell beat are hashed out in cultured cells. These cells provide the basis (proof of principle) that theories work. These are also a single population of cells that are tested. Just muscle cells that comprise part of the heart can be grown in isolation. It is easy to test how these cells grow and work, but it is isolated and no other neighboring cells are involved or communicating with our heart muscle cell when it’s in culture systems. So, while tissue culture helps ID how heart muscle cells work, it is not an entire heart organ and may behave differently.
Many things can be tested initially in culture to determine if the hypothesis is correct and cells work the way scientists think they do. Say a new drug is developed. This drug could be designed to attack a particular target, for instance a certain protein in the cell that is involved in cell proliferation. First, the drug will be tested in tissue culture cells to see if it is effective, to learn more about how it works and if there could be potential unintentional side effects. Our new drug can effectively attack its target and stop cell growth, but it could also attack other targets and cause other outcomes. After the drug is tested and appears to be effective, animal models are next. FDA approved drugs must be tested in animals in order to get approval to be tested or used in humans. Many things can change when a whole organism is being tested including if the drug is effective. So, tissue culture serves an important role in labs but it isn’t everything and can be very different from what happens when the drug is given to humans.
Many things can be tested initially in culture to determine if the hypothesis is correct and cells work the way scientists think they do. Say a new drug is developed. This drug could be designed to attack a particular target, for instance a certain protein in the cell that is involved in cell proliferation. First, the drug will be tested in tissue culture cells to see if it is effective, to learn more about how it works and if there could be potential unintentional side effects. Our new drug can effectively attack its target and stop cell growth, but it could also attack other targets and cause other outcomes. After the drug is tested and appears to be effective, animal models are next. FDA approved drugs must be tested in animals in order to get approval to be tested or used in humans. Many things can change when a whole organism is being tested including if the drug is effective. So, tissue culture serves an important role in labs but it isn’t everything and can be very different from what happens when the drug is given to humans.
Friday, June 25, 2010
patents and informed consent
I recently read two very interesting articles. The first was a column in the Philadelphia Inquirer, “DNA in court” (Faye Flam, Monday, June 21, 2010, Business section). The article was discussing the impending court battle arguing the validity of the Myriad Genetics patent on the DNA sequence of breast cancer genes, BRCA1 and BRCA2 (the name stands for BReast CAncer)*. The second was an article, “Immortal Cells, Enduring Issues”, in the Johns Hopkins Magazine (Dale Keiger, Summer Issue 2010) about the newly published book about the 1st human cells to be grown in a lab, HeLa cells.**
In 1980, Congress enacted the Dole-Bayh Act that provided universities and non-profit organizations with intellectual property rights to inventions developed within their institutions. This has been a boon for scientists, universities and non-profits. It has allowed scientists to patent their ideas and to earn their due rewards. No question, they deserve it! It has also allowed for patents to be issued on DNA sequences. This brings us back to the Myriad Genomics issue. In 2000-2001 Myriad Genomics and the University of Utah Research Foundation obtained a patent on the BRCA1 sequence and a genetic test to detect mutations in the DNA sequence that is associated with increased risk for developing breast and ovarian cancers. Myriad Genomics is not alone; there are greater than 2000 DNA sequences of genes in the body have been patented. This brings up many important ethical issues surrounding ownership of the DNA that exists in every cell of everyone’s body and about donating cells or DNA to studies. The latter topic is the subject of the Hopkins Magazine article.
A recently published book discusses the ethical issues surrounding the methodology used in obtaining cervial cancer cells and in the development of HeLa cells in a Hopkins lab. HeLa cells are named after a woman in Baltimore, Henrietta Lacks, who suffered from cervical cancer. When she went into the hospital, doctors removed the tumor and used part of it to establish an immortalized cell line that is still utilized today. The HeLa cell was the first cells to be maintained outside the body in what is called tissue culture which has revolutionized modern molecular medicine. Using and testing these cells has led to enormous revelations and advancements in science. The importance of this cell line and what has been discovered because of it is truly immeasurable!
The ethical issues raised by the HeLa case are still hotly debated. Probably the most significant surrounds the issue of informed consent. Whenever you volunteer for a scientific experiment or donate tissues/cells/DNA for a scientific endeavor, you provide consent for the scientist to use your material for an expressed purpose. The scientist is required to inform you about how the material will be used in a way that you will understand to which you allow the materials to be used in that way. You are informed and provide consent. The problem arises when laws change over time or technology advances to the point where the scientific questions being asked were not even conceived of at the time of consent. Informed consent was very different in the 1950s when Henrietta Lacks was alive than today. How does a scientist get consent if the idea or technology doesn’t exist or won’t exist for many, many years? Is it ok to use DNA obtained for other purposes?
Obviously, I alone cannot answer these questions, but they point to how much science is so much a part of our lives and how much we need to keep talking about these issues. As an update, recently, the US District court ruled to invalidate the patent held by Myriad and placing the patents for all the other genes in jeopardy as well. Myriad is appealing, which might mean that this case will make it to the Supreme Court. It will be interesting to see where this leads.
* DNA is found in every cell of our bodies and contains the code for the proteins that complete the function of that particular cell (ie. heart cells contain some different proteins than skin cells but all the proteins are encoded by the same DNA sequence that is found in every cell). DNA is made up of 4 units (or bases) that string together in a specific order (or sequence). Mutations in certain genes have been shown to contribute to the development a disease. Mutations in the BRCA1 and 2 sequence are associated with increasing the risk of developing breast or ovarian cancer.
** HeLa cells were the first immortalized human cells to grow in a lab (in culture). Unlike other previous cells, HeLa didn’t die after a few days like other cells.
In 1980, Congress enacted the Dole-Bayh Act that provided universities and non-profit organizations with intellectual property rights to inventions developed within their institutions. This has been a boon for scientists, universities and non-profits. It has allowed scientists to patent their ideas and to earn their due rewards. No question, they deserve it! It has also allowed for patents to be issued on DNA sequences. This brings us back to the Myriad Genomics issue. In 2000-2001 Myriad Genomics and the University of Utah Research Foundation obtained a patent on the BRCA1 sequence and a genetic test to detect mutations in the DNA sequence that is associated with increased risk for developing breast and ovarian cancers. Myriad Genomics is not alone; there are greater than 2000 DNA sequences of genes in the body have been patented. This brings up many important ethical issues surrounding ownership of the DNA that exists in every cell of everyone’s body and about donating cells or DNA to studies. The latter topic is the subject of the Hopkins Magazine article.
A recently published book discusses the ethical issues surrounding the methodology used in obtaining cervial cancer cells and in the development of HeLa cells in a Hopkins lab. HeLa cells are named after a woman in Baltimore, Henrietta Lacks, who suffered from cervical cancer. When she went into the hospital, doctors removed the tumor and used part of it to establish an immortalized cell line that is still utilized today. The HeLa cell was the first cells to be maintained outside the body in what is called tissue culture which has revolutionized modern molecular medicine. Using and testing these cells has led to enormous revelations and advancements in science. The importance of this cell line and what has been discovered because of it is truly immeasurable!
The ethical issues raised by the HeLa case are still hotly debated. Probably the most significant surrounds the issue of informed consent. Whenever you volunteer for a scientific experiment or donate tissues/cells/DNA for a scientific endeavor, you provide consent for the scientist to use your material for an expressed purpose. The scientist is required to inform you about how the material will be used in a way that you will understand to which you allow the materials to be used in that way. You are informed and provide consent. The problem arises when laws change over time or technology advances to the point where the scientific questions being asked were not even conceived of at the time of consent. Informed consent was very different in the 1950s when Henrietta Lacks was alive than today. How does a scientist get consent if the idea or technology doesn’t exist or won’t exist for many, many years? Is it ok to use DNA obtained for other purposes?
Obviously, I alone cannot answer these questions, but they point to how much science is so much a part of our lives and how much we need to keep talking about these issues. As an update, recently, the US District court ruled to invalidate the patent held by Myriad and placing the patents for all the other genes in jeopardy as well. Myriad is appealing, which might mean that this case will make it to the Supreme Court. It will be interesting to see where this leads.
* DNA is found in every cell of our bodies and contains the code for the proteins that complete the function of that particular cell (ie. heart cells contain some different proteins than skin cells but all the proteins are encoded by the same DNA sequence that is found in every cell). DNA is made up of 4 units (or bases) that string together in a specific order (or sequence). Mutations in certain genes have been shown to contribute to the development a disease. Mutations in the BRCA1 and 2 sequence are associated with increasing the risk of developing breast or ovarian cancer.
** HeLa cells were the first immortalized human cells to grow in a lab (in culture). Unlike other previous cells, HeLa didn’t die after a few days like other cells.
Thursday, June 17, 2010
genome at 10 years
Welcome! We at n3 science communications are interested in talking about science. We created this blog to start a dialog about current scientific topics. Since the sequencing of the human genome is celebrating its 10 year anniversary, we thought we'd start there. Please share your thoughts and comments! We'd love to hear from you!
There has been much talk recently about sequencing the genome and the treasure trove it was supposed to provide. Yes, it has been 10 years since the first human genome was sequenced and no, we don't have tailored medicines and the answers to what genes are altered in every disease state, but we have come a long way! It is truly amazing to listen to discussions about how in a matter of a few years, we will be able to sequence a person's genome for $300 - 500. (The first genome sequenced cost billions!) Quite honestly, that is truly remarkable. While there is a long way to go before we understand all the ins and outs of how genes control our health and well-being, it is awe-inspiring to think that it was only 1952 when Watson and Crick identified the structure of DNA.
Scientifically, we now understand that there are less genes encoded in the DNA than originally thought. Researchers now have a tremendous amount of information about a particular gene and can understand how that gene contributes to the development of disease. We also understand how similar and dissimilar genes can be. This aids in identifying what genes could be targeted when new medicines are developed and how to target just one gene and not other genes that are closely related. This will eventually lead to a decrease in unwanted drug side effects. Beyond the health and science benefits of this project, the computer technology developed to complete this project was astounding.
There will be a lot of work to do, but with the latest technology, speed and accuracy of sequencing is improving. This does begin many conversations about ethics and how to handle this data. It also drives home to me just how important understanding science and what this means really is in our society.
There has been much talk recently about sequencing the genome and the treasure trove it was supposed to provide. Yes, it has been 10 years since the first human genome was sequenced and no, we don't have tailored medicines and the answers to what genes are altered in every disease state, but we have come a long way! It is truly amazing to listen to discussions about how in a matter of a few years, we will be able to sequence a person's genome for $300 - 500. (The first genome sequenced cost billions!) Quite honestly, that is truly remarkable. While there is a long way to go before we understand all the ins and outs of how genes control our health and well-being, it is awe-inspiring to think that it was only 1952 when Watson and Crick identified the structure of DNA.
Scientifically, we now understand that there are less genes encoded in the DNA than originally thought. Researchers now have a tremendous amount of information about a particular gene and can understand how that gene contributes to the development of disease. We also understand how similar and dissimilar genes can be. This aids in identifying what genes could be targeted when new medicines are developed and how to target just one gene and not other genes that are closely related. This will eventually lead to a decrease in unwanted drug side effects. Beyond the health and science benefits of this project, the computer technology developed to complete this project was astounding.
There will be a lot of work to do, but with the latest technology, speed and accuracy of sequencing is improving. This does begin many conversations about ethics and how to handle this data. It also drives home to me just how important understanding science and what this means really is in our society.
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