Daily Archives: December 23, 2019

Psychology has been heavily criticized lately for its research practices. Most commonly discussed is the so-called replication crisis,whereby efforts to replicate classic and non-classic studies alike have often failed. Psychology has become transfixed on this issue, and at times even paralyzed. But there are clear signs that things are changing for the better.

Researchers, journals, and organizations are pushing for greater transparency, cooperation, data sharing, and pre-registration of research hypotheses, methods, and data analytic strategies. This must all surely be good for the science of psychology.

It is clear that psychology bears the brunt of the criticism about replication. Truth be told, however, many (if not most) fields of science have difficulties replicating their findings. John Ioannidis wrote a very highly read and cited paper on this problem called "Why Most Published Research Findings Are False" that has shaken science deeply. Most people concentrate on psychology, and psychologists certainly like pointing their fingers at themselves, but the deeper we dig, the more we find that this is not a problem limited to psychology, but rather is common in other sciences, including medicine and chemistry.

Psychology certainly has its faults. But psychology is also at the forefront of addressing concerns about research methods, inferential statistics, and best practice recommendations.

Replication failures happen for many reasons, including low statistical power and small samples (that generally fail to generalize to the wider world). One of the problems with trying to reproduce psychological findings concerns the sheer complexity of the human mind. (As a psychologist, and especially as a social psychologist, Im often envious of researchers in other disciplines who study more simple phenomena, particularly those that dont react to being studied!).

It is also important to keep in mind that psychology generally attempts to explain relatively universal truths about humanity, but in reality, we only look at a very narrow slice of humanity, what researchers call WEIRD (Western, Educated, Industrialized, Rich, Democratic) participants. As Henrich et al. note, Within the field of psychology, 95 percentof psychological samples come from countries with only 12percentof the worlds population (Arnett 2008).

Is psychology the only offender in this regard? Sadly, no. Apparently, studies that map the human genome are similarly focused on a very narrow slice of humanity. As of 2009, about 96percentof genomic data was derived from people of (White) European background.

And things have not improved much since. Devaney (2019) reports that our present understanding of the human genome has been largely derived from samples who are White European (78 percent), with very little from those with African (2 percent) or Hispanic or Latin American (1 percent) ancestry. This is staggeringone would reasonably expect that researchers attempting to map humanitys genomes would sample a broad swathe of humanity.

So what is the problem with understanding the psychology of humanity from observing predominantly White, European people in educated and enriched environments? And what is the problem with only using such people to map the human genome?

The question almost answers itself, doesnt it?

We should be invested in examining the full diversity of humanity if we want to understand the full diversity of humanity. One wouldnt study only penguins if one wished to learn about birds as a general category. The same applies to the study of humans, whether their psychological makeup or their genetics.

Failure to examine the diversity of a species is fraught with problems and possible dangers when trying to make claims about the nature of that species. After all, wed risk concluding that birds cant fly if we spent our research energies only in the Antarctic.

Originally posted here:
Variety Is the Spice of Life (In Research Too) - Psychology Today

This article, written byMichael Mackley, Dalhousie University, originally appeared on The Conversation and is republished here with permission:

Youve likely heard about direct-to-consumer DNA testing kits. In the past few years, at-home genetic testing has been featured in the lyrics of chart-topping songs, and has helped police solve decades-old cold cases, including identifying the Golden State Killer in California.

Even if you dont find a DNA testing kit under your own Christmas tree, theres a good chance someone you know will.

Whether youre motivated to learn about your health or where your ancestors came from, it is important to understand how these tests work before you spit in the tube.

While exciting, there are things that these genetic testing kits cannot tell users and important personal implications that consumers should consider.

Health, traits and ancestry kits

My main area of research is around clinical genome sequencing, where we look through all of a persons DNA to help diagnose diseases. With a PhD in genetics, I often get questions from friends and family about which direct-to-consumer genetic test they should buy, or requests to discuss results. Most questions are about two types of products: ancestry and health kits.

The most popular ancestry kit is from AncestryDNA. These kits are aimed at giving users insight into where their ancestors might be from. They can also connect users with family members who have used the service and have opted into having their information shared. Another option is Living DNA, which has a smaller dataset but provides more precise information on the U.K. and Ireland.

The most popular health kit is from 23andMe. Depending on the users preference, results include information on predispositions for diseases such as diabetes and Alzheimers, as well as on the likelihood of having certain traits such as hair colour and taste. This company also offers ancestry analysis, as well as ancestry and trait-only kits that dont provide health information. The kit offered by the newer MyHeritage DNA also provides a combined ancestry and health option.

There are other kits out there claiming to evaluate everything from athletic potential to relationship compatibility. But gift-buyers beware: for most of these, in contrast to those above, the evidence is seriously lacking.

How these tests work

For all of these tests, customers receive a kit in the mail. The kits contain instructions for collecting a saliva sample, which you mail back to the company for analysis.

During this analysis, these popular tests do not look at the entire genome. Instead, they employ single nucleotide polymorphism (SNP) genotyping. As humans we all share 99.9 per cent of our DNA. SNPs are essentially what is left: all of the points at which we can differ from our neighbour, making us unique. SNP genotyping looks at a subset of these sites to survey the users genome.

These SNPs are then compared to reference datasets of individuals with known conditions or ancestry. Most results are based on the SNPs shared with a given group. For example, if your results say that you are 42 per cent Southeast Asian, its because 42 per cent of your SNPs were most likely to have come from a group in the reference dataset labelled Southeast Asian. The same goes for traits and health conditions.

How they differ from clinical tests

Direct-to-consumer genetic tests are not a substitute for clinical assessment. The methods used differ dramatically from what is done to diagnose genetic diseases.

In a clinical setting, when suspicion of a genetic condition is high, entire genes are often analyzed. These are genes where we understand how changes in the DNA cause cellular changes that can cause the disease. Furthermore, clinical assessment includes genetic counselling that is often key to understanding results.

In contrast, findings from direct-to-consumer genetic tests are often just statistical links; there is commonly no direct disease-causing effect from the SNPs.

Users may interpret a result as positive, when the risk increase is only minimal, or entirely false. These tests can also give false reassurance because they do not sequence genes in their entirety and can miss potentially harmful variants.

Before you spit in a tube, stop and think

These tests are exciting: they introduce new audiences to genetics and get people thinking about their health. Theyre also helping to build vast genetic databases from which medical research will be conducted.

But for individual users, there are important caveats to consider. Recent reports have questioned the accuracy of these tests: identical twins can receive different results. Furthermore, a lack of diversity in the reference data has caused particular concern regarding accuracy of results for ethnic minorities.

There are also concerns about the way these tests emphasize racial categories that science considers to be social constructs and biologically meaningless.

A recent paper in the British Medical Journal suggests four helpful questions for users to consider. First, users should ask themselves why they want the test. If it is to answer a medical question, then they should speak with their doctor. Users should also think about how they might feel when they receive results containing information they would rather not know.

Users should also consider issues around security and privacy. It is important to read the fine print of the service youre using, and determine whether youre comfortable sharing personal information, now and in the future.

In Canada, policies around genetics have not always kept up with the science. At present, direct-to-consumer genetic testing is unregulated. And, although Canadians have legislative protections against genetic discrimination, those laws are being challenged in the courts, and could change.

Finally, it may also be worth discussing DNA testing with relatives. We share half of our genome with our immediate family members, and smaller fractions with more distant relatives. Genetic results not only affect us, but our family.

Bottom line: Its all for fun

Some users may feel they learn more about themselves. For others, results may bring people closer together not a bad outcome for the holiday season.

At the end of the day, these genetic testing kits are for entertainment: they should not be used to assess health risk in any meaningful way.

If you have any questions related to your health or a genetic disease, discuss these with your family doctor or a suitable health-care professional.

Michael Mackley, Junior Fellow, MacEachen Institute for Public Policy and Governance; Medical Student, Dalhousie University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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BEYOND LOCAL: DNA tests might be a fun holiday gift, but beware of the hype - ThoroldNews.com

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, is hosting an R&D Day today beginning at 8am Eastern Time. During the event, Sangamo executives and scientists plan to provide updates across the Companys clinical and preclinical pipeline, as well as an overview of manufacturing capabilities to support clinical and commercial supply. A live webcast link will be available on the Events and Presentations page of the Sangamo website

The talent, R&D capabilities, manufacturing expertise, and operations infrastructure we have brought to Sangamo have enabled us to advance a genomic medicine pipeline that spans multiple therapeutic areas and now also extends into late-stage development, said Sandy Macrae, CEO of Sangamo. As we make progress in clinical development, we gain insights into the use of our technology and are applying those insights as we advance new programs, such as the gene therapy for PKU and the genome regulation candidates for CNS diseases we are announcing today.

Macrae continued: We will continue to pursue a dual approach of retaining certain programs for our proprietary pipeline while also establishing pharmaceutical partnerships to gain access to therapeutic area expertise and financial, operational, and commercial resources. Strategic collaborations will be a particularly important consideration as we advance programs for diseases affecting large patient populations.

R&D Day updates on clinical and preclinical pipeline programs:

Gene therapy product candidates for hemophilia A, Fabry disease, and PKU

SB-525 is a gene therapy product candidate for hemophilia A being developed by Sangamo and Pfizer under a global development and commercialization collaboration agreement. The transfer of the SB-525 IND to Pfizer is substantially completed. Pfizer is advancing SB-525 into a Phase 3 registrational study in 2020 and has recently begun enrolling patients into a Phase 3 lead-in study.

At R&D Day, Sangamo executives are presenting data from the SB-525 program which were recently announced at the American Society of Hematology (ASH) annual meeting.

The cassette engineering, AAV engineering and manufacturing expertise which Sangamo used in the development of SB-525 are also being applied to the ST-920 Fabry disease program, which is being evaluated in a Phase 1/2 clinical trial, as well as to the newly announced ST-101 gene therapy program for PKU, which is being evaluated in preclinical studies with a planned IND submission in 2021.

Engineered ex vivo cell therapy candidates for beta thalassemia, kidney transplantation, and preclinical research in multiple sclerosis (MS)

Sangamo is providing an overview of the Companys diversified cell therapy pipeline this morning. Cell therapy incorporates Sangamos experience and core strengths, including cell culture and engineering, gene editing, and AAV manufacturing. At R&D Day, Sangamo scientists today are reviewing the early data presented this month at ASH from the ST-400 beta thalassemia ex vivo gene-edited cell therapy program, which is being developed in partnership with Sanofi.

Sangamo is also providing updates on the companys CAR-TREG clinical and preclinical programs. CAR-TREGS are regulatory T cells equipped with a chimeric antigen receptor. Sangamo is the pioneer in CAR-TREGS, which may have the potential to treat inflammatory and autoimmune diseases. TX200 is being evaluated in the STEADFAST study, the first ever clinical trial evaluating a CAR-TREG cell therapy. Tx200 is being developed for the prevention of immune-mediated organ rejection in patients who have received a kidney transplant, a significant unmet medical need. Results from this trial will provide data on safety and proof of mechanism, building a critical understanding of CAR-TREGS in patients, and may provide a gateway to autoimmune indications such as Crohns disease and multiple sclerosis (MS). Sangamo is also presenting preclinical murine data demonstrating that CAR-TREGS accumulate and proliferate in the CNS and reduce a marker of MS.

In vivo genome editing optimization

Clinical data presented earlier this year provided evidence that Sangamo had successfully edited the genome of patients with mucopolysaccharidosis type II (MPS II) but also suggested that the zinc finger nuclease in vivo gene editing reagents were under-dosed using first-generation technology. Sangamo has identified potential improvements that may enhance the potency of in vivo genome editing, including increasing total AAV vector dose, co-packaging both ZFNs in one AAV vector, and engineering second-generation AAVs, ZFNs, and donor transgenes.

Genome regulation pipeline candidates targeting neurodegenerative diseases including Alzheimers and Parkinsons

Sangamo scientists today are presenting data demonstrating that the companys engineered zinc finger protein transcription factors (ZFP-TFs) specifically and powerfully repress key genes involved in brain diseases including Alzheimers, Parkinsons, Huntingtons, ALS, and Prion diseases. Sangamo is advancing its first two genome regulation programs toward clinical development:

Sangamo scientists are also presenting data demonstrating progress in the development of new AAV serotypes for use in CNS diseases.

Manufacturing capabilities and strategy

Sangamo is nearing completion of its buildout of a GMP manufacturing facility at the new Company headquarters in Brisbane, CA. This facility is expected to become operational in 2020 and to provide clinical and commercial scale manufacturing capacity for cell and gene therapy programs. The Company has also initiated the buildout of a cell therapy manufacturing facility in Valbonne, France. Sangamos manufacturing strategy includes in-house capabilities as well as the use of contract manufacturing organizations, including a long-established relationship with Thermo Fisher Scientific for clinical and large-scale commercial AAV manufacturing capacity.

R&D Day webcast

A live webcast of the R&D Day, including audio and slides, will be available on the Events and Presentations page of the Sangamo website today at 8am Eastern Time. A replay of the event will be archived on the website.

About Sangamo Therapeutics

Sangamo Therapeutics is committed to translating ground-breaking science into genomic medicines with the potential to transform patients lives using gene therapy, ex vivo gene-edited cell therapy, and in vivo genome editing and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Sangamo Forward Looking Statements

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of United States securities law. These forward-looking statements include, but are not limited to, the therapeutic potential of Sangamos product candidates; the design of clinical trials and expected timing for milestones, such as enrollment and presentation of data, the expected timing of release of additional data, plans to initiate additional studies for product candidates and timing and design of these studies; the expected benefits of Sangamos collaborations; the anticipated capabilities of Sangamos technologies; the research and development of novel gene-based therapies and the application of Sangamos ZFP technology platform to specific human diseases; successful manufacturing of Sangamos product candidates; the potential of Sangamos genome editing technology to safely treat genetic diseases; the potential for ZFNs to be effectively designed to treat diseases through genome editing; the potential for cell therapies to effectively treat diseases; and other statements that are not historical fact. These statements are based upon Sangamos current expectations and speak only as of the date hereof. Sangamos actual results may differ materially and adversely from those expressed in any forward-looking statements. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to dependence on the success of clinical trials; the uncertain regulatory approval process; the costly research and development process, including the uncertain timing of clinical trials; whether interim, preliminary or initial data from ongoing clinical trials will be representative of the final results from such clinical trials; whether the final results from ongoing clinical trials will validate and support the safety and efficacy of product candidates; the risk that clinical trial data are subject to differing interpretations by regulatory authorities; Sangamos limited experience in conducting later stage clinical trials and the potential inability of Sangamo and its partners to advance product candidates into registrational studies; Sangamos reliance on itself, partners and other third-parties to meet clinical and manufacturing obligations; Sangamos ability to maintain strategic partnerships; competing drugs and product candidates that may be superior to Sangamos product candidates; and the potential for technological developments by Sangamo's competitors that will obviate Sangamo's gene therapy technology. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamos operations. This presentation concerns investigational drugs that are under preclinical and/or clinical investigation and which have not yet been approved for marketing by any regulatory agency. They are currently limited to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. Any discussions of safety or efficacy are only in reference to the specific results presented here and may not be indicative of an ultimate finding of safety or efficacy by regulatory agencies. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission on March 1, 2019 and Sangamo's Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 that it filed on or about November 6, 2019. Except as required by law, we assume no obligation, and we disclaim any intent, to update these statements to reflect actual results.

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Sangamo Highlights Advancements in Genomic Medicine Pipeline and Expanded R&D and Manufacturing Capabilities at R&D Day - Business Wire

The building housing the Ministry of Health, Labor and Welfare is seen in Tokyo's Chiyoda Ward. (Mainichi/Kimi Takeuchi)

TOKYO -- Japan will perform full-genome analysis on medical samples from as many as 93,000 people under an action plan revealed by the country's health ministry.

The blood, cancer cells and other samples are held at hospital and research institute biobanks around the country, and will be prioritized for analysis for a number of years. Special priority will be placed on samples from some 22,000 people expected to be useful for research in hopes of discovering details of cancer and intractable diseases and drugs for their treatment.

Analyzing a person's entire genome could allow researchers to identify genetic causes or trigger mechanisms for certain diseases that may not be apparent from looking at just one part of the patient's genes. There are also hopes that building a database combining results of the full-genome analysis of cancer patients with clinical information will help Japan formulate broader cancer-fighting measures.

According to the action plan, cancer patient samples make up some 65,000 of the total set for full genome analysis, while about 28,000 are from people with other intractable conditions. For the analysis, a sample genome needs to be compared with data such as a healthy blood sample and the genetic makeup of the patient's parents. That being the case, the plan will in fact require full analysis of some 168,000 genomes. Furthermore, new samples from the patients will also be obtained for analysis.

In the coming years, blood and cancer cell samples from the 22,000 people stored at biobanks in the country will be given priority for analysis, with the subjects' consent. These initial studies will seek the genetic causes of cancers with low 5-year survival rates, rare and hereditary cancers as well as intractable illnesses that could not be identified through partial genome analysis.

However, there remain many unanswered questions about whether and to what degree information from full-genome breakdowns will lead to new and effective diagnostic, treatment, and drug options. The Ministry of Health, Labor and Welfare will examine the results from studies using the priority samples, and clarify a target number of specimens needed for analysis in cases where the development of diagnostic and treatment methods can be expected.

Full-genome analysis medical research projects are proceeding apace under government-backed programs in other countries. Britain, for example, began full-genome analysis for 100,000 people with cancer or rare diseases in 2018. The U.K. government is aiming to analyze the genomes of a million people by 2023.

(Japanese original by Sooryeon Kim, Lifestyle and Medical News Department)

Link:
Japan gov't plans full-genome analysis on 93000 people to boost medical research - The Mainichi