Tuesday May 21, 2013
Last week researchers at Oregon Health and Science announced they had made human embryo clones using skin cells. The technique was similar to the one used to clone Dolly, the sheep, almost 20 years ago. Why has it taken so long to clone humans? Are we that different than sheep?
In fact, cloning resarch has a long history and there has been pretty continuous progress with mammalian cloning over the past 25 years. Mice, dogs, cats, and even camels have been cloned. The latest result in Oregon is only the most recent discovery in a field that has been gradually unraveling the processes of how a single cell can develop into complex organism for over 100 years starting with work on sea urchins.
Of course, this recent work by the lab in Oregon has received much more attention than most other cloning experiments because it involves humans. The experiment sparked immediate controversy as soon as it was published. However, as a recent USA Today article points out, a clone is basically an identical twin so there is nothing particularly strange about them.
Also, the Oregon group did not actually create a human clone, just a cloned embryo. While the work has brought us close to being able to fully clone a human being, this is not really the main purpose of the study. Based on the group's previous work with primates, the embryo would not likely even be able to develop into a human. We still do not known enough about development to successfully produce a cloned person.
This gap in our understanding, though, is sort of the point. Although only time will tell if this technique will ever find useful clinical applications, the embryos produced by this process will be very useful to generate embryonic stem cells for biomedical research. The technique provides an essential research tool to investigate the process of development and differentiation that enables one cell to produce a whole person. It provides a basis on which to build a more sophisticated understanding of this miraculous transformation. In the end, it is this deeper knowledge that will provide new and better medical treatments.
You can read more information on this cloning breakthrough and the history of cloning research in two recently posted articles:
Monday May 13, 2013
Back in February the Supreme Court heard arguments from farmer Vernon Bowman on why he didn't need to pay royalties to Monsanto for growing their patented GMO soybeans that have been genetically modified to be resistant to the pesticide in Round-Up. Today, Mr. Bowman lost his case when the Court unanimously ruled against him. He owes Monsanto $84,000 in royalties.
Bowman bought uncharacterized soybeans intended as animal feed from a local supplier. He admited that he thought most of the generic soybeans would probably be Round-Up ready GMO varieties even though they weren't labeled that way or sold as crop seeds. Since he didn't specifically buy Round-Up ready seeds, however, he argued that he didn't infringe on Monsanto's patent. In fact, he claimed it was the seeds themselves that replicated the patented invention.
All the Justices disagreed with Bowman. "But we think that blame-the-bean defense tough to credit." noted Justice Elena Kagen in delivering the Court's opinion. "Bowman was not a passive observer of his soybeans' multiplication; or put another way, the seeds he purchased...did not spontaneously create eight successive soybean crops....Bowman devised and executed a novel way to harvest crops from Roundup Ready seeds without paying the usual premium."
Justice Kagen points out that the Court's opinion is based understanding that, "Under the doctrine of patent exhaustion, the authorized sale of a patented article gives the purchaser, or any subsequent owner, a right to use or resell that article. Such a sale, however, does not allow the purchaser to make new copies of the patented invention."
For more on the ruling, see a summary on ScienceInsider.
Tuesday May 7, 2013
The lab of Rudolf Jaenisch, who developed the first transgenic mouse in 1974, has developed a new approach to genetically engineer mice in just weeks, rather than years which are currently needed. This new technique does not rely on engineering embryonic stem (ES) cells, but rather, directly introduces the genetic changes in developing mouse embryos. In addition to making production of transgenic mice and rats for laboratory research faster and easier, it should also work with other types of organisms whose embryonic cells are difficult to engineer and manipulate.
The new approach takes advantage of a unique response bacterial developed as a defense against invading viruses. Bacteria can target and cut the DNA of invading viruses. To do this, they use short sequences of DNA that match some part of the DNA of the invading virus. Many bacteria seem to have a "catalog" of short stretches of DNA that match parts of many different types of viruses. These regions of DNA were dubbed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) when they were first discovered.
Researchers found that they could co-opt this bacterial defense system to target and inactivate specific genes in more advanced non-bacterial cells. To do this, they only needed to introduce the gene that cuts the targeted viral DNA in bacteria--the CRISPR-associated protease (Cas). Basically, it seems that almost any gene in most cells can be cut by introducing DNA that makes the Cas protein and a CRISPR construct with a short sequence that recognize some small part the gene. Even though a cell will fix a gene that has been cut, it does not get fixed correctly (because of the way Cas cuts it). Then, the gene will no longer work, so it has been "knocked out".
Inactivating or "knocking out" genes is a common approach researchers use to understand how particular genes function and also generate mice or rat strains that model various human diseases. One of the big difficulties of engineering animals with certain genes knocked out, though, is that almost all genes come in pairs--one from each parent. Both copies of a gene need to be inactivated to fully knockout a gene. Unless the knock out technique is very efficient, this is rare. However, the CRISPR approach seems to be exceptionally effective.
In a Cell publication this week, the researchers in Dr. Jaenisch's lab describe how they were able to simultaneously and specifically knock out two genes with a single injection of a mouse embryo. Further, they also used the technique to produce embryonic mouse stem cells with disruptions of 5 distinct genes simultaneously. Mice produced using these embryonic stem cells would then carry all 5 of these mutations.
For a more information, you can read the press release from the Whitehead Institute at MIT describing the paper.
Saturday May 4, 2013
Thirteen of the world's leading stem cell researchers just published a statement in the European Molecular Biology Organization (EMBO) Journal expressing alarm about initiatives to deregulate stem cell therapies. Recent actions by the Italian government allowing unapproved stem cell treatments precipitated the researchers' statement.
Last year, the Italian Medicines Agency or AIFA (equivalent to the FDA in the US), ordered a halt to unapproved stem cell treatment program being carried out at the Brescia Civilian Hospital on the basis that there was no scientific evidence for its effectiveness. The treatment was being done under the direction of the Stamina Foundation, founded by Davide Vannoni, a psychology professor at the University of Udine. According to an article in Nature, 32 terminally ill patients, mostly children, were being treated using the therapy. However, the treatment was never approved by AIFA.
Protests in response to the interruption of the treatment prompted Italy's Minister of Health, Renaldo Balduzzo to override the AIFA order in March. Despite the strong objections in an open letter to the Minister from thirteen Italian scientists researching stem cells, the Italian Parliament, in one of its last acts before new elections, issued a decree allowing the Stamina therapy to continue.
As a result, the authors of the EMBO article felt the need to emphasize the importance of "strident regulation" of medical applications of stem cells to ensure "the translation of science into effective therapies." They point to the current situation in Italy, as well as recent stem cell regulatory battles in the US and a case in Germany in which unregulated stem cell treatments resulted in death, as examples of how rules set out by regulatory bodies such as the FDA and EMA have so far been effective in protecting patients from serious risks associated the indiscriminate use of unproven therapies, and voice their concern that these rule seem to be changing for stem cell therapies.
In reference to the current case in Italy, the article notes that, "The treatment, offered by a private non-medical organization, may not be safe, lacks a rationale, and violates current national laws and European regulation." Also, the authors understand the augment for reinstating treatment in the Italian case was that "safety is not a concern in the face of severely ill children or adults, for whom there are no therapeutic alternatives." However, they emphasize that:
"Compassion only applies when one offers a safe and potentially effective remedy. That a remedy is effective must be supported by published clinical data. If such data are not available, there is no legitimate assumption of effectiveness in the individual patient, and therefore no 'compassion'."
You can read more about the article in the press release from EMBO.