. — As a child in Hilo, one of the less touristy parts of Hawaii, Jennifer A. Doudna felt out of place. She had blond hair and blue eyes, and she was taller than the other kids, who were mostly of Polynesian and Asian descent.
“I think to them I looked like a freak,” she recently recalled. “And I felt like a freak.”
Her isolation contributed to a kind of bookishness that propelled her toward science. Her upbringing “toughened her up,” said her husband, Jamie Cate. “She can handle a lot of pressure.”
These days, that talent is being put to the test.
Three years ago, Dr. Doudna, a biochemist at the University of California, Berkeley, helped make one of the most monumental discoveries in biology: a relatively easy way to alter any organism’s DNA, just as a computer user can edit a word in a document.
The discovery has turned Dr. Doudna (the first syllable rhymes with loud) into a celebrity of sorts, the recipient of numerous accolades and prizes. The so-called Crispr-Cas9 genome editing technique is already widely used in laboratory studies, and scientists hope it may one day help rewrite flawed genes in people, opening tremendous new possibilities for treating, even curing, diseases. But now Dr. Doudna, 51, is battling on two fronts to control what she helped create. While everyone welcomes Crispr-Cas9 as a strategy to treat disease, many scientists are worried that it could also be used to alter genes in human embryos, sperm or eggs in ways that can be passed from generation to generation. The prospect raises fears of a dystopian future in which scientists create an elite population of designer babies with enhanced intelligence, beauty or other traits. Scientists in China reported last month that they had already used the technique in an attempt to change genes in human embryos, though on defective embryos and without real success.
In April 2015 a team of Chinese scientists reported in a little known journal, Protein & Cell, the use of CRISPR/Cas9 to cleave and then repair the HBB gene in nonviable human embryos. The mutated form of HBB causes B-thalassemia, a potentially fatal blood disease. To say the experiment prompted controversy is an understatement. It was published on the heels of two high-profile commentaries in Nature and Science, both of which urged caution about using CRISPR/Cas9 and other technologies to edit the human germline; the Nature authors went so far as to recommend a stop of experiments precisely like the one reported in Protein & Cell. The Liang et al. paper seemed to fly in the face of the recommendations. Though the researchers used triponuclear human embryos (an essential fact missed by some of the breathless reporting in the days after), they designed the experiment as a test of a possible therapeutic strategy. If eventually proven safe, a diseased embryo would be corrected using CRISPR/Cas9 with the intent of eventually making a healthy baby. Importantly, the authors reported notable off-target effects of CRISPR-based gene editing, low efficiency of homologous recombination directed repair (HDR), mosaicism, and unwanted mutations. They concluded:
Taken together, our data underscore the need to more comprehensively understand the mechanisms of CRISPR/Cas9-mediated genome editing in human cells, and support the notion that clinical applications of the CRISPR/Cas9 system may be premature at this stage.
Further Genomics Research:
Genomcis and LC (liquid Chromatography) -MS/MS (Tandem Mass) mass spectrometry analysis is What’s Next For A Breast Cancer Cure. Barron Medical Journal has found we now have the know how and the systems to detect breast cancer genes and now at this year’s show BMJ has found one of the major advances in science that have been around for over a Hundred years MS mass Spectrometry (MS) is an analytical technique that produces spectra (singular spectrum) of the masses of the molecules comprising a sample of material. The great news about MS is we can now validate our genomic gene finding. The next step is to get this technology out of the University
centers in to commercial use. Here are some success stories on breast cancer and MS Mass Spectrometry.
Barron’s Medical Journal breast cancer focus was amplified right outside of Washington, DC USA Where The National Institute Of Health Director Francis Collins gave the rights and say so of one of the most important genes in the fight for breast cancer. The HSP70 the gene protein cancer cells kept alive…..More on the background for Henrietta Lacks in the next paragraph. Tumor differentiation factor (TDF) is our line of discussion in this article. We now have genomics which tells us that genes GRP78 and HSP70 are key in Indentifying and solving breast cancer. In molecular genomics we also have a tool called Mass spectrometry which allows scientist to verify our gene analysis.
In others words cancer cells taken without consent from A African American Women is used to identify bio Markers used in the scientific puzzle "A Breast Cancer Cure". Henrietta Lacks (August 1, 1920 – October 4, 1951) (sometimes erroneously called Henrietta Lakes, Helen Lane or Helen Larson) was an African-American woman who was the unwitting source of cells (from her cancerous tumor) which were cultured by George Otto Gey to create an immortal cell line for medical research. This is now known as the HeLa cell line. On January 29, 1951, Henrietta went to Johns Hopkins Hospital because she felt a knot inside her. It all started when she asked her cousins to feel her belly, asking if they felt the lump that she did. Her cousins assumed correctly that she was pregnant. But, after giving birth to her fifth child, Joseph, Henrietta started bleeding abnormally and profusely. Her local doctor tested her for syphilis, which came back negative, and referred her to Johns Hopkins.
Johns Hopkins was their only choice for a hospital, since it was the only one in proximity to them that treated black patients. Howard Jones, her new doctor, examined Henrietta and the lump in her cervix. It was like nothing he had ever seen before. He cut off a small part of the tumor and sent it to the pathology lab. Soon after, Jones discovered she had a malignant epidermoid carcinoma of the cervix Stage 1 (cervical cancer). Lacks was treated with radium tube inserts, which were sewn in place. After several days in place, the tubes were removed and she was released from Johns Hopkins with instructions to return for X-ray treatments as a follow-up. During her radiation treatments for the tumor, two samples of Henrietta's cervix were removed— a healthy part and a cancerous part— without her permission.[10] The cells from her cervix were given to Dr. George Otto Gey. These cells would eventually become the HeLa immortal cell line, a commonly used cell line in biomedical research.
In significant pain and without improvement, Lacks returned to Hopkins on August 8th for a treatment session, but asked to be admitted. She remained at the hospital until the day of her death. Though she received treatment and blood transfusions, she died of uremic poisoning on October 4, 1951 at the age of thirty-one. A subsequent partial autopsy showed that the cancer had metastasized throughout her entire body.
Henrietta Lacks was buried without a tombstone in a family cemetery in Lackstown, a part of Clover in Halifax County, Virginia. Her exact burial location is not known, although the family believes it is within feet of her mother's gravesite. Lackstown is the name of the land that has been held by the (black) Lacks family since they received it from the (white) Lacks family, who had owned the ancestors of the black Lackses when slavery was legal. Many members of the black Lacks family were also descended from the white Lacks family. A row of boxwoods separates the graves of whites from those of the blacks buried in the family cemetery.For decades, Henrietta Lacks' mother had the only tombstone of the five graves in the family cemetery in Lackstown, and Henrietta's own grave was unmarked. [11][12] In 2010, however, Dr. Roland Pattillo of the Morehouse School of Medicine donated a headstone for Lacks after reading The Immortal Life of Henrietta Lacks. The headstone, which is shaped like a book, reads:
Henrietta Lacks, August 01, 1920-October 04, 1951. In loving memory of a phenomenal woman, wife and mother who touched the lives of many. Here lies Henrietta Lacks (HeLa). Her immortal cells will continue to help mankind forever. Eternal Love and Admiration, From Your Family
The cells from Henrietta's tumor were given to researcher George Gey, who "discovered that [Henrietta's] cells did something they'd never seen before: They could be kept alive and grow." Before this, cells cultured from other cells would only survive for a few days. Scientists spent more time trying to keep the cells alive than performing actual research on the cells but some cells from Lacks's tumor sample behaved differently than others. George Gey was able to isolate one specific cell, multiply it, and start a cell line. Gey named the sample HeLa, after the initial letters of Henrietta Lacks' name. As the first human cells grown in a lab that were "immortal" (they do not die after a few cell divisions), they could be used for conducting many experiments. This represented an enormous boon to medical and biological research.
HeLa by a researcher at the hospital helped answer the demands of the 10,000 who marched for a cure to polio shortly before Lacks' death. By 1954, the HeLa strain of cells was being used by Jonas Salk to develop a vaccine for polio To test Salk's new vaccine, the cells were
In the avalanche of commentary that followed was a blink-and-you-missed-it defense of the decision to publish the paper by Xiaoxue Zhang (2014), the editor of Protein & Cell. The editorial is a fascinating read, encapsulating the social and ethical tensions surrounding germline editing. Perhaps stung by criticism the experiment was unethical , Zhang says, “With extraordinary care, consideration and deliberation, Protein & Cell has decided to publish in this issue a scientific study that reports CRISPR-based gene-editing of human tripronuclear zygotes.” Zhang goes on to justify why the research was published in the first place: The editorial decision to publish this study should not be viewed as an endorsement of this practice nor an encouragement of similar attempts, but rather the sounding of an alarm to draw immediate attention to the urgent need to rein in applications of gene-editing technologies, especially in the human germ cells or embryos.
From an ethics and policy perspective, how should we measure the Protein & Cell experiment and the decision to publish it? A framework for social responsibility such as the model proposed by Sankar and Cho in their target article might help, but would likely need to include more stakeholders than just bench scientists. Decisions to publish do not occur in isolation. Researchers, reviewers, ethics advisors, and editorial boards all have an opportunity to dialogue during the review process, so the responsibilities to publish socially controversial research are shared. In her commentary, Bovenkirk argues for a “thick” accounting of social responsibility in the sciences and this seems to make sense here. With respect to the Protein & Cell publications, it appears that important elements of the Sankar and Cho framework are already in play. Categories of justification, reasoning to identify harms and benefits, reflexivity, and timing—specifically, designing an experiment ostensibly to uncover the risks the authors enumerate in the conclusions—are on full view in both the research paper and in the editor’s justification. Of course we must trust that other stakeholders were part of the “extraordinary care, consideration and deliberation” and that those deliberations would be fully available to outside observers. But there is a nuance about the Protein & Cell example that is worth a closer look. In their commentary, Mertes and Penning argue that because the Liang et al research showed the dangers of any clinical use of the technology, an outcry about whether the research should have been published is misplaced. After all, both the Science and Nature essays called for more research to determine the safety and efficacy of CRISPR/Cas9 for future clinical use. Wasn’t this precisely what the experts ordered?
It would seem so. But an argument could be made—something hinted at but not directly addressed in Greeley and Charo’s lighthearted target article—that the Chinese experiment was frivolous. The results in the Protein & Cell study were anticipated in animal studies and indeed predicted by the Nature commentary. Some CRISPR/Cas9 researchers believe that the experiment provided little scientific insight. The raises the question of whether we should publish the technical feat of human germline editing or work that moves the field forward in significant ways. So what do we do now that the Protein & Cell study is out? Follow-on experiments become increasingly derivative and are worth exponentially less to science. At what point do such experiments become data-gathering exercises rather than answers to fundamental questions about human development and disease? Given the controversial nature of human germline research, what experiments investigating disease type, embryo stage, culture conditions and other incremental advances should go forward? For example, gene-editing technologies can either knock out (cleave a gene of interest) or knock in (insert a gene of interest). The Liang and colleagues experiment was technically a knock out study. The researchers edited the HBB gene and then asked whether genetic repair pathways recruited an endogenous gene, HBD, to replace the cleaved sequence. Suppose the next CRISPR/Cas9 experiment using human embryos attempts a knock in or gene replacement strategy. Does this represent a frivolous or an important use of the technology? There are some pathways to take with respect to this question. In a recent commentary in Nature Biotechnology, we offer examples of in vitro research that is ethically and scientifically justified, such as probing questions of early human development and infertility. Such research is covered under existing oversight mechanisms and regulation.
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