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FDA Docket No. 2003N-0529 - Amending the MedWatch Forms to Collect Postmarketing Adverse Event Data Relating to Race and Ethnicity
http://www.fda.gov/OHRMS/DOCKETS/98fr/03-30300.htm
I. Background
A. FDA Regulations
FDA regulations require sponsors to present an analysis of data according to demographic subgroups (age, gender, race), as well as an analysis of modifications of dose or dosage intervals for specific subgroups (21 CFR 314.50(d)(5)(vi)(a)) in certain marketing applications.
B. MedWatch Forms
Medwatch Forms FDA 3500 and 3500A are used by voluntary and mandatory reporters, respectively, to collect information on adverse events, product quality problems, and medication errors that occur during marketed use of FDA-regulated products. The MedWatch forms collect demographic and other information about patients in the patient information section (box A), which includes specific data fields for age (box A.2), sex (box A.3), and weight (box A.4). The forms do not, however, include a unique field to capture data on race and ethnicity. Race and ethnicity data can be collected in box B.7 of the MedWatch forms, however, other information is collected in box B.7, including information on preexisting medical conditions (e.g., allergies, pregnancy, smoking and alcohol use, hepatic/renal dysfunction). In addition, the information captured in this section is in a narrative format and cannot be searched efficiently to extract race and ethnicity data. Thus, current placement of race and ethnicity data in box B.7 of the MedWatch forms limits the ability of FDA to analyze postmarketing adverse event data by race and ethnicity.
C. Office of Management and Budget (OMB) Recommendations and FDA Draft Guidance
In 1997, OMB issued recommendations for the collection and use of race and ethnicity data by Federal agencies (Statistical Policy Directive No. 15, Race and Ethnic Standards for Federal Statistics and Administrative Reporting, 1997). In the Federal Register of January 30, 2003, FDA made available for comment a draft guidance for industry entitled ``Collection of Race and Ethnicity Data in Clinical Trials' (68 FR 4788). In the draft guidance, FDA recommends the use of standardized OMB race and ethnicity categories for data collection in clinical trials. The agency's recommendations are intended to ensure consistency in the analyses of demographic subsets across studies and to help evaluate potential differences in the safety and efficacy of pharmaceutical products among population subgroups.
With respect to collection of the data, in the draft guidance, the agency provided the following recommendations:
1. A two-question format should be used for requesting race and ethnicity information, with the ethnicity question preceding the question about race.
2. Study participants should self-report race and ethnicity
information whenever feasible, and individuals should be permitted to designate a multiracial identity. When the collection of self-reported designations is infeasible (e.g., because of the subject's inability to respond), we recommend the information be requested from a first-degree relative or other knowledgeable source.
3. For ethnicity, the following minimum choices should be offered:
[sbull] Hispanic or Latino
[sbull] Not Hispanic or Latino
4. When race and ethnicity information is collected separately, the following minimum choices should be offered for race:
[sbull] American Indian or Alaska Native
[sbull] Asian
[sbull] Black or African American
[sbull] Native Hawaiian or Other Pacific Islander
[sbull] White
5. In certain situations, as directed in OMB Directive 15, more detailed race and ethnicity information may be desired (e.g., White can reflect origins in Europe, the Middle East, or North Africa; Asian can reflect origins from areas ranging from India to Japan). If more detailed characterizations of race or ethnicity are collected to enhance data consistency, these characterizations should be traceable to the five minimum designations for race and two designations for ethnicity listed under numbers 3 and 4 in section I.C of this document.
D. ICH Guidance
In 1998, as part of an international effort among Japan, the European Union, and the United States to harmonize technical requirements for pharmaceutical drug development and regulation (ICH (International Conference on Harmonisation)), FDA published a guidance entitled ``E5 Ethnic Factors in the Acceptability of Foreign Clinical Data' (63 FR 31790, June 10, 1998). The E5 guidance provides recommendations to permit the clinical data collected in one region to be used in the registration or approval of a drug or biological product in another region, while allowing for the influence of ethnic factors. The E5 guidance defines ethnic factors that could affect drug response in terms of both intrinsic and extrinsic issues. Because there is the potential for differences in the safety and efficacy of pharmaceutical products among population subgroups, the E5 guidance provides a general framework for how to evaluate medicines with regard to ethnic factors.
II. Scope of Discussion
In view of the background information presented in section I of this document, FDA is requesting comment on the advantages and disadvantages of collecting race and ethnicity data in postmarketing adverse event reports. FDA is also seeking feedback on whether the MedWatch forms should be amended to collect this data based on the standardized categories described in section I.B of this document. Specific comments are being sought on the following questions:
1. Should the MedWatch forms (Forms FDA 3500A and 3500) be amended with a special field or fields to capture adverse event data on race and ethnicity?
2. Should MedWatch race and ethnicity data distinguish between self-reported and observer-reported designations? If so, how should the designations be captured?
3. Would collection of race and ethnicity data on the MedWatch forms have an impact on the ICH E2B guidance relating to the electronic submission of adverse event reports (``E2B Data Elements for Transmission of Individual Case Safety Reports' (63 FR 2396 at 2397, January 15, 1998))?
4. What is the financial impact associated with adding a special field or fields to the MedWatch forms to collect data on race and ethnicity?
Dated: November 27, 2003.
End of draft document
Now it should come as no surprise that most reponses to the FDA received to date were not in favor of the proprosals. I have added links to the individual responses and selected a couple of interesting comments from these (the NIH response is reproduced in full).
December 11, 2003
Zymed Laboratories comments
http://www.fda.gov/ohrms/dockets/dailys/04/jan04/010704/03N-0529-emc00001.txt
Surely you jest.
(Note: I think this guy can expect a pretty hard time with any future FDA returns from Zymed Laboratories lol)
January 4, 2004
Wyeth comments
http://www.fda.gov/ohrms/dockets/dailys/04/jan04/013004/03n-0529-c00002-vol1.pdf
January 8,2004
3M Pharmaceuticals comments
February 2, 2004
Bristol Myers Squibb comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021204/03n-0529-c00003-vol1.pdf
February 4, 2004
PhRMA comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021204/03n-0529-c00004-vol1.pdf
February 4, 2004
Colgate Palmolive comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021204/03n-0529-c00005-vol1.pdf
February 4, 2004
Merck comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03N-0529-emc00002-01.pdf
We recommend against including a field to capture ethnicity data for a number of reasons. First, OMB's "Revisions to the Standards for the Classification of Federal Data on Race and Ethnicity" (62 FR 58782, October 30, 1997) points out that the concept of ethnicity includes numerous cultural and environmental factors. Therefore, we believe that it lacks sufficient definition to be useful as a basis for any implications concerning differences in drug response...
February 5, 2004
GlaxoSmithKline comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021204/03n-0529-c00007-vol1.pdf
February 5, 2004
National Medical Association comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03N-0529-emc00004-01.doc
Yes, MedWatch should distinguish between self-reported and observer-reported designations. To account for multiple races, as with the Office of Management and Budget (OMB) Directive 15, we recommend that individuals be allowed to identify “more than one category of race” as a means of reporting diverse ancestry.
February 6, 2004
Biotechnology Industry Organization comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03N-0529-emc00005-01.pdf
February 6, 2004
AdvaMed comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021204/03n-0529-c00006-vol1.pdf
February 6, 2004
Plasma Protein Therapeutic Association comments
http://www.fda.gov/ohrms/dockets/dailys/04/feb04/021104/03N-0529-emc00003-01.pdf
March 4, 2004
NIH comments
http://www.fda.gov/ohrms/dockets/dailys/04/mar04/030104/03N-0529_emc-000007-01.pdf
NIH Comments on the FDA Guidance Document 2003N-0529 Related to Racial and Ethnic Coding on MedWatch Forms to Collect Postmarketing Adverse Event Data
The NIH is pleased to provide the following comments in response to the FDA Notice: Amending the MedWatch Forms to Collect Postmarketing Adverse Event Data Relating to Race and Ethnicity [Docket No. 2003N-0529]. The NIH supports the collection of race and ethnic data as it relates to post-marketing Adverse Events. This approach will complement requirements for inclusion of minorities and adverse event reporting in the clinical research supported by the NIH in the pre-marketing environment. Nevertheless, the NIH would like to offer a number of comments and considerations along with background material that describes the data collection approach currently required for all NIH supported clinical trials. There would certainly be advantages to the development of a parallel system and we would be pleased to participate in discussions along those lines. Dr. Carlos Caban in the Office of Extramural Research at 301-435-2687 could help coordinate those discussions.
Please find below a summary of NIH comments including a list of advantages and disadvantages to the proposed data collection; comments related to the four questions that appeared in the Scope of Discussion section of the Notice; and finally a background section on related NIH requirements.
Summary of NIH comments
Data from post-market experience is collected to better understand the implications of adverse events on the overall safety of persons receiving any new treatment. Because of the understandable limits on the participation in most clinical trials and the potential for poor representation of individual subgroups, the proposed post-marketing data collection will be very important. Race and ethnicity has been shown to be an important although limited variable in understanding an event and identifying susceptible components of a treatment population. Race and ethnic classifications can clearly be correlated with the incidence and prevalence of a number of different diseases and heritable traits. There are also correlates with treatment-related behavior and access to health services, which may be important in a post-marketing environment.
It is frequently pointed out; however, that race and ethnic classifications are imprecise and can be poor surrogates of biological and genetic traits. Where practical, it might be more useful to record data by ancestral group as suggested in the FDA posting. Frequently, however, individuals, especially those in the United States, may not know their ancestry with a high degree of certainty. Lastly, clinicians and policy makers must use care in generalizing individual or small numbers of adverse events to all individuals with the same ancestry. Any information collected must be treated cautiously. In spite of the shortcomings, the advantages of collecting data on race and ethnicity clearly outweigh the disadvantages.
Advantages-
Having data on race and ethnicity may help to evaluate trends and differences in the safety and efficacy of certain drugs or treatment among sub-populations.
Collecting such information may be helpful in identifying at-risk groups.
Having data on race and ethnicity may also help to explain the interaction of this information with other demographics (age, sex, and weight - questions 2-4) and relevant history/pre-existing medical conditions (question 7), and how these factors interplay in drug response and efficacy.
Data on race and ethnicity provide a measure of the social context that influences outcome and may be a surrogate for a complex demographic profile that integrates culture/SES/beliefs/health knowledge and that can be followed for trends.
The genetic basis of diseases has the underlying principle that there are subpopulations that bear more of the risk or susceptibility for certain diseases than the general population. It is clear from historical as well as more recent data that there are variations across racial/ethnic groups in terms of treatment responses and risk (particularly in terms of drug response/kinetics as a function of differences in drug metabolism among racial/ethnic groups, the classic being G6PD deficiency being more common in African Americans, and leading to difficulty metabolizing certain medications).
Another reason to record these categories is to monitor whether MedWatch reporting is being under- or over-utilized for any particular group.
Disadvantages-
The data on race and ethnicity is imprecise and may be especially misleading if an individual identifies with 2 or more races.
Considering the lack of precision and relatively low rates of correlation with specific genetic and biological markers, there is the possibility of overgeneralizing events and altering treatment policies beyond the specifically susceptible group.
Having race and ethnicity information may facilitate post hoc pharmacogenomic analyses, but the usefulness will be dependent on the availability of single nucleotide polymorphisms (SNPs) or other markers particular for each ethnic category that would allow differentiation. Most ethnic/racial populations are so diverse that any broadly-based analysis could weaken the benefit of collecting this information.
May raise ethical concerns about the labeling or profiling of individuals based on their race.
The patient may be suspicious of why race information is requested .
Possible increased burden on the investigator or company.
With the proposed change, many would perceive race and ethnicity as tightly linked to biological processes, when, as OMB states, the categories are not to be interpreted as scientific or anthropological in nature.
Question 1: Should the MedWatch forms (Forms FDA 3500A and 3500) be amended with a special field or fields to capture adverse event data on race and ethnicity?
Yes, the MedWatch forms should be amended with special fields to capture race and ethnicity including detailed race and ethnicity information, in certain situations. (See the discussion on collection of information in international settings below) The collection of the race and ethnicity data would be advantageous given the emphasis now placed on post-marketing data as agents receive accelerated approval. This is especially true for groups that are under-represented in the clinical trials that lead to approval. Important differences based, for example, on genetic polymorphisms may not become apparent until after approval, and post-marketing data collection would be as important as pre-marketing adverse event (AE) reporting in the identification of trends and leads. Both race and ethnicity should be captured in domestic populations. Failure to collect and track this information limits the ability of individuals, in consultation with their health care provider, to determine whether a specific product is appropriate for them. It will help indicate the presence of a genetic, cultural, logistical, or environmental role for outcomes. NIH requires the collection of race/ethnicity data from individuals in all clinical research projects that it supports. NIH also requires reporting of target data and annual cumulative enrollment data by sex/gender and race/ethnicity using the two question format. A parallel data collection in the post-marketing period could be very useful. (See the background section at the end of this document)
Specific Issues Related to International Reporting-
The FDA ICH E5 – Guidance on Ethnic Factors in the Acceptability of Foreign Clinical Data – defines ethnic factors that affect response in terms of both intrinsic and extrinsic issues, and provides a general framework for how to evaluate medicines with regard to their sensitivity to racial/ethnic factors. Differences in racial/ethnic factors have the potential to adversely affect some populations. These distinctions are important when the OMB racial/ethnicity categories are to be applied to foreign populations. The categories may be too broad to be useful in international studies, without additional information, and the collection of data according to these categories may not meet the ICH E-5 provision for identifying ethnic factors that may affect response to treatment.
The data may not be sensitive enough for determining the scientific relevance of the ethnic differences in disease progress and response to treatment. Race/ethnicity reporting may only be appropriate for U.S.-based adverse events. Clearly it must be acknowledged that the only scientific way to distinguish differences is to relate all results to genomic distinctions.
If FDA decides to amend its MedWatch forms to capture racial and ethnic data in international settings, the choices for ethnicity and race as outlined in I.C.3. and I.C.4. are not sufficient. The addition of other subcategories that may be collapsed into the required ethnicity and race categories may well be needed. Since the pharmacological value of these categories stems from their loose overlap with ancestry, we recommend that the link be more explicit in the choices for all situations. For example, as alluded to in I.C.5., “White” alone is not an appropriately informative category; “European Ancestry,” “Middle Eastern Ancestry,” and “North African Ancestry” should be used instead or in combination with the OMB Racial and Ethnic categories especially in international settings. While these terms may not cleanly branch from the five choices FDA outlined in I.C.4., these terms have more relevance to adverse drug reactions than the subjective and frequently misunderstood terms “Black” and “White.” Also, individuals should be able to choose more than one ancestry, similar to the ability to designate a multi-racial identity (I.C.2.). This may be more difficult logistically, and it will add statistical complexity. However, people have complex ancestries and this should be accounted for within any system attempting to collect this type of data. Ideally, data on the geographic origin of the individual’s ancestors at least two generations back should be collected. If these recommendations are too onerous, then the utility of collecting information through the OMB categories will be significantly diminished from a biological standpoint. Although potential correlations between adverse event data and racial and ethnic reporting may emerge, it will be impossible to draw meaningful biological conclusions from any observed trends.
Depending on how other countries report race and ethnicity overall, such data may not be generalizable. However, it may be useful in international reporting of post-marketing adverse events among broad ethnic or racial group categories. NIH has experienced real concerns when collecting race/ethnicity information in the international environment. In the U.S., race/ethnicity data is self-reported. The US OMB categories for race and ethnicity frequently lack meaning, cultural sensitivity and applicability when collected in other countries.
The following example may be instructive:
We recently went through lengthy explanations on the best way to collect race and ethnicity data with a PI who had a clinical site in Brazil. In order to comply with NIH policy, the 'foreign PI' is asked to design a culturally sensitive tool for collecting the data (via study volunteer self report) and then to take the reported ethnic, racial, and gender data and "fit it" the best way possible into the NIH Inclusion Enrollment Report Table for annual progress reports. As you can imagine, this presents all sorts of difficulties. We learned that in Brazil, for example, 66% of people think of themselves as mixed race; 40% claim to be white; and 4% claim themselves to be black. Apparently on birth certificates and military forms they recognize a category neither black nor white, called "Pardo" ....so 60% of people in the census reports conceive of themselves as Pardo.
Question 2: Should MedWatch race and ethnicity data distinguish between self reported and observer-reported designations? If so, how should the designations be captured?
MedWatch data should distinguish between self-reported and observer-reported designations. The possibility for misreporting a person's race or ethnicity based on observation is great. Self-reporting should be the standard. If self-reporting is not possible, then the observer most likely to know the ancestry of the individual should report the race and ethnicity information (such as a first-degree relative per I.C.2.). However, whatever process by which this observer is identified should be specified in the regulations and followed consistently. It is important that all researchers follow the
same procedure for assigning race, ethnicity and ancestry in order to avoid compounding sources of error to what is, by its very nature, an imprecise measurement. Such distinctions should be made so that data can be compared based on self-reporting versus observational reporting. Observational reporting should be clearly marked, and if possible and not unduly burdensome, should be updated should self-reporting become possible. Possibly, a separate check-box should be placed next to the ethnicity and race section for self-reported race/ethnicity or observer-reported race/ethnicity.
Question 3: Would collection of race and ethnicity data on the MedWatch forms have an impact on the ICH E2B guidance relating to the electronic submission of adverse event reports (``E2B Data Elements for Transmission of Individual Case Safety Reports' (63 FR 2396 at 2397, January 15, 1998))?
Yes. Race and ethnicity data are not specifically addressed in the E2B Data Elements Guidance. The race/ethnicity data elements could be added in two ways. First, the data elements could be added under category “B.1. Patient Characteristics” as separate data fields. User guidance would need to describe how to handle United States data versus data from foreign sites in terms of the OMB race/ethnicity categories and the two question format. Separate electronic data fields in this section could enable analysis of the role of race/ethnicity as it relates to other information in the form. The number of additional data elements would be minimal, since the individual is reporting his/her own data. Alternatively, the information request could be included under category “B.5. Narrative Case Summary and further information” in a manner similar to item B.7. of the current MedWatch form 3500. User guidance would be needed here also to describe how to handle US data versus data from foreign site. It is not clear what the compliance level is for filling out item B.7 for race/ethnicity data in MedWatch form 3500. However, it would require more staff work to receive the paper form and transfer it to an electronic database for analysis. The ICH E2B Guidance was prepared under the auspices of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for human use (ICH). These changes would require working with the group to implement any suggested changes, and will take time. Since it will be guidance, and not mandatory, the database could be incomplete and bias any analysis.
Question 4: What is the financial impact associated with adding a special field or fields to the MedWatch forms to collect data on race and ethnicity?
Changing the forms to add a special field or fields to collect data on race and ethnicity would have a financial impact that varies on how it is implemented. Any change will require the development of educational venues and detailed instructions to facilitate broad understanding and compliance. If the forms are available electronically, the costs would include revising the electronic form as well as the underlying database to accept the data on the forms. If paper forms will also be used, then replacing the old forms with new forms may have a financial impact. There will also be costs associated with modifying relevant databases in addition to data coding costs associated with paper forms. In all cases, there are quality control issues that need to be built in to ensure the data is as accurate as possible.
Here is the relevant part of the Research Capital agreement as described in the 10Q filed on 20 November 2003:
http://12.40.163.150/Archives/edgar/data/1169417/000118206303000278/gm10qsb.htm
(5) Note Payable - Affiliate
On April 9, 2003 the Company converted $1,010,500 in advances and $67,081 of accrued interest into a convertible promissory note in the amount of $1,077,581. The note bears interest at 8% per annum and is due on January 1, 2005. The note may be converted into common shares of the Company as follows:
a. The unpaid principal in whole or in part together with accrued interest shall at the option of the holder be converted into the class of the Company's shares on the same terms and conditions applicable to any investors in a financing agreement. The holder may elect to negotiate separate terms and conditions however the unpaid balance will not be payable in cash, but convertible only into shares of the Company. For the purposes of this calculation the aggregate value of the Company's shares received by the holder in conversion shall be determined by subtracting $1,000,000 from the unpaid original principal balance of the note, which remains unpaid at the time of conversion. A financing agreement is defined as the receipt by the Company of a least $1,500,000 of net cash proceeds from the sale of capital stock.
b. The unpaid principal in whole or in part together with accrued interest shall be converted into shares if the Company realizes revenue of $1,500,000 during the period commencing April 9, 2003 and ending on December 31, 2004. The price per share shall be determined as provided in c below. The unpaid balance will not be payable in cash but convertible only into shares of the Company. For the purposes of this calculation the aggregate value of the Company's shares received by the holder in conversion shall be determined by subtracting $1,000,000 from the unpaid original principal balance of the note, which remains unpaid at the time of conversion.
c. If no financing agreement has occurred by December 31, 2004 and/or the Company has not realized the requirements of a and b above the holder may elect to convert the unpaid principal balance and accrued interest into the number of common shares of the Company determined by dividing the unpaid balance by the average bid price of the Company's common stock for the previous 30 trading days. The unpaid balance will not be payable in cash but convertible only into shares of the Company.
(6) Subsequent Event
On October 15, 2003, we executed a subscription agreement with Research Capital, LLC in which we have agreed from November 1, 2003 to October 1, 2004, to offer to sell to Research Capital, as an Investor, our restricted common stock at a 40% discount of the previous month's average closing bid price up to an aggregate amount of $500,000. Under the agreement, Research Capital agrees to purchase a minimum of $10,000 of the shares each month, representing a total minimum investment of $120,000.
This is an interesting project:
http://www.unm.edu/~jadab/research/
The Caribbean African Ancestry Project (CAAP) is an ongoing population genetic study of the Caribbean. The goals of this research include identifying the numerous West African ethnic groups and identifying other populations that contributed to present-day African- derived Caribbean populations using molecular genetic techniques.
Elsewere on the site is a list of the genetic markers that will be used to estimate ancestry and admixture, and Shriver et al are referenced in the Background (Related Research) section.
That is interesting isn't it. More potential for synergies between the incubator companies.
Adenovir, the main advantages will relate to research and technology transfer - which can work both ways of course. Both USF and Moffit (who are very closely involved with the USF) are keen to accelerate the commercialization of their technology in conjunction with industrial partners. Being physically located at USF is going to pay real dividends IMO.
Here's another article from the USF research site that gives a bit more context:
http://www.research.usf.edu/absolutenm/templates/newro.asp?articleid=181&zoneid=29
USF’s Growing Research Profile in Health Sciences
By Dr. M. Ian Philips
Thursday, March 04, 2004 - Look around campus, or just listen. What you see and hear is the sound of construction, of growth and progress.
There's the new Natural Science Building, new student housing, a new athletic facility, an extension to the Alumni Building, a new clinic and Nursing building, and even a new parking garage. This was all planned to give USF a real campus life.
We are currently phasing in new strategies in the way we do research. Evidence of our growth can be found in The Chronicle (Feb. 6, 2004, p. 17). Jumping up 17 positions from last year, USF was among the top 100 universities leading in NIH funding. Last year alone, we received $37 million from NIH. Overall, we exceeded over $250 million in total research funding, a 29% increase from last year. The Health Center jumped 23% to over $110 million. However, we are still short of high-quality lab space, we lack high-tech equipment cores, and we need to recruit more outstanding faculty and graduate students.
To fill the need for Class-A laboratory space, we are building the Interdisciplinary Research Building (IDRB) in the Research Park. There will be no departments, and no colleges owning the space. The IDRB will be open to all research faculty who qualify. This building will be for high-quality funded research groups who thrive on interdisciplinary research. A Steering Committee, made up of myself, Rod Casto, Carl Carlucci, Louis Martin-Vega, Bob Anderson, Stan Kranc, Jackie Cattani, Gary Littman, Phil Marty, Jack Pledger, and some yet to be named faculty, will oversee the best use of the building.
I consider that the new Nanotechnology Building, so ably pursued by Mike Kovac and Stan Kranc, is also part of this new spirit of interdisciplinary research. We are purchasing some key items of equipment, transmission electron microscopes, scanning electron microscopes, and real-time PCRs for a core in the IDRB. Cores are essential for a high tech research environment. The research building will be attached to the new incubator building, the Tampa Bay Technology Incubator, to foster start-up companies in close contact with USF faculty researchers. Dr. Rod Casto, Associate Vice President for Research & Technology Development, heads this effort. His skill and experience in academia and business are paying off as he continues to sign up tenants.
The majority of USF's research income is derived from the Health Sciences Center. With a new Interim Vice President for Health Sciences and Dean of the College of Medicine, Dr. Robert Belsole, and his Associate Vice President for Health Sciences Research, Dr. Phil Marty, The Health Sciences Center brings in almost half of USFs research funding from grants. There are many signs of increased value of research to the HSC faculty. Over $6 million from a Health Resources and Services Administration (HRSA) grant has gone into renovating new research labs. There are emerging four areas of research excellence in the medical field—in neuroscience and behavior, in cardiovascular science, in infectious disease, and, of course, in cancer at the Moffitt Cancer Center & Research Institute. Our relationship with Moffitt continues to grow stronger, based on mutual respect. Dr. Robert Engelman, of our staff, has brought in $2.7 million in grants to build a new vivarium to be shared with Moffitt. We continue to enjoy the research successes of the Department of Interdisciplinary Oncology in the recently opened, spectacular research space at the Stabile Research Building.
A symposium on cardiovascular research in February drew together some 50 USF researchers in the Health Sciences Center. The Annual HSC Research Day was vibrant and exciting with a theme on Functional Genomics, Biomedical and Heart Peptides. At All Children's Hospital, there is already an active group of pediatric cardiology researchers at the Children's Research Institute. We hope that the expanded Pepin Heart Institute being built at University Community Hospital will join with us in creating a strong center for research and the treatment of cardiovascular disease. We have the chance with Tom Pepin to develop a major heart treatment Center of Excellence in this region.
Neuroscience continues to thrive in the areas of stem-cell regeneration and Alzheimer's research. The new Florida Alzheimer's Center & Research Institute has been funded and the director, Dr. Hunt Potter, has already begun to hand out research grants on Alzheimer's. Together, with our nationally ranked Department of Psychology; the Departments of Psychiatry, Neurology, and Neurosurgery; and the James A. Haley VA Hospital, USF has a lot of neurons working on brain and behavior diseases.
There is a link between the heart and the brain in research because of the intense interest and reputation USF has in cell therapy. Using stem cells derived from bone marrow and from umbilical cords for regeneration and repair, Paul Sanberg, Juan Sanchez-Ramos and their collaborators are repairing diseased brains or hearts.
In the College of Public Health and the College of Nursing, there is an explosion of population-based research. Jim Studnicki and Don Berndt have amassed a warehouse of health related data and ways to mine it. A new department of global health has the purpose of training health professionals in identifying and controlling emerging diseases. This area also impacts on Homeland Security and training health professionals and early responders to deal with new treats. The Center for Biodefense is a major source of interdisciplinary research and applied solutions.
USF is totally in tune with the NIH roadmap. The roadmap urges us to bring discoveries from the lab more quickly to the clinic. We have a duty to help the citizens of the nation that have put so much of their money and trust in NIH and other research agencies. USF Health Sciences is pushing their priorities for a healthier Florida and USA. As the NIH roadmap goes, so grows NIH research at USF.
How about this work?
http://www.research.usf.edu/absolutenm/templates/newro.asp?articleid=173&zoneid=4
Searching for Cancer's Self-Destruct Button
By Kevin Hale
Cells die in two ways: either injurious agents kill them or they are induced to commit suicide. Dr. Hong-Gang Wang is interested in the latter. You could say, he's a cell suicide expert.
Wang, who’s an assistant professor in the Interdisciplinary Oncology Program at Moffitt Cancer Center and a researcher in the Drug Discovery Program, understands that in every cell of every individual, there resides a process of their own self-destruction.
One of the main goals of the Drug Discovery Program is to identify and validate novel targets for the discovery of safe and efficacious anticancer drugs. This is accomplished through outstanding research at the basic level by people like Dr. Wang.
Here’s the thing about cells, they’re like nuclear submarines: incredibly powerful, for the most part self-sufficient and extremely dangerous in the hands of the enemy. The secrets they contain, which would be DNA in this case, must be protected at all costs. It’s so incredibly important that our cells be loyal that, like any good military vessel with top secret documents, they’ve been programmed with a self-destruct sequence. This sequence is also known as apoptosis.
The pattern of events in death by suicide is so orderly in cells that the process is often called programmed cell death or PCD. The cellular machinery of programmed cell death turns out to be as intrinsic to the cell as, say, mitosis.
Wang explained that you can see apoptosis in action in various aspects of our lives. The formation of the fingers and toes of the fetus requires the removal, by apoptosis, of the tissue between them. The sloughing off of the inner lining of the uterus at the start of menstruation occurs by apoptosis. The formation of the proper connections between neurons in the brain requires that surplus cells be eliminated by apoptosis.
Wang, however, is interested in the process by which the body uses programmed cell death to destroy cells that represent a threat to the integrity of the organism. Cells infected with viruses, cells with DNA damage, and most importantly for him and Moffitt, the cancer cells that are killed by the process of apoptosis.
A cell that has incurred an initial genetic alteration is believed to be programmed to die by default. Sometimes, however, the initial genetic alteration or the tampering of the DNA of the cell will overexpresses death inhibitor genes and increases its chances to survive.
“Our laboratory studies the role of programmed cell death and cell cycle checkpoints in malignancy. Much of the work in our laboratory focuses on the intracellular signaling pathways mediated by the Bcl-2 family of proteins for programmed cell death and apoptosis.”
Basically, one way to trigger a cell’s self-destruct mechanism is to send out a signal to a cell that trips an internal alarm. This alarm triggers a set of events within the cell that starts with a gene called Bcl-2. This gene was discovered as the translocated locus in a B-cell leukemia (hence the name). This gene, which encodes a protein that blocks apoptosis and allows survival, have been found overexpressed in human tumors. Specifically, B-cell leukemias and lymphomas, express high levels of Bcl-2 and blocks the apoptotic signals they receive.
And that’s the key. Wang wants to stop or break through this shield of Bcl-2 that these cancer cells hold desperately on to for life. He’s searching for any “molecule that suppress the anti-apoptotic Bcl-2 protein or alternatively that activate the pro-apoptotic protein Bax.” It’s promising research at the Drug Discovery Program and Wang hopes (very soon) to start assisting several cells into the next life.
Hong-Gang Wang. That name is familiar from 2002:
http://www.floridahightech.com/rpt2002/med_research.htm
A Model System for Cancer Pharmacogenomics
Project Leader: Hong-Gang Wang
Industry Partners: DNAPrint Genomics
Total Allocated Funds: $305,000
Corridor Investment: $99,000
Private Match, In-Kind: $206,000
http://isis.fastmail.usf.edu/oed/match/01awards.htm
Wang, Hong-Gang. "A model system for cancer pharmacogenomics." Grant Amount: $99,000. Partner companies: DNAPrint Genomics.
Layman's Abstract: DNA print genomics is enabling the medical application of human population genomics to help prevent, define and diagnose disease. With the University of South Florida will develop a cell based model system to determine the variable response to two widely used anti-cancer compounds. The resulting product will constitute a powerful tool for developing genomics-based pharmaco-predictive tools that will form the foundation of the emerging personalized medical market.
Incidentally, these are the selection criteria used by the Tamp Bay Technology Incubator, which applying companies must meet or exceed.
http://www.incubator.usf.edu/AdmissionCriteriaApplication.pdf
Tampa Bay Technology Incubator staff and Advisory Board uses the following criteria:
• A technology based company operating in the Tampa Bay area
• Assistance requested can be met with the existing resources of the University and
partners
• Capable entrepreneurial management in place and/or identification of necessary
leadership for success
• Proprietary technologies are most desirable, but not required.
• Benefit from the services offered by the incubator
• Sufficient working capital and/or identified sources of funds for at least 18 months
• Desire to leverage the programs/services of the University, incubator and community
partners
• An acceptable written business plan or significant documentation to complete a
business plan within 3 to 6 months
• Technology product(s) or service(s) that will be market ready in less than 36 months
• Apparent probability of being successful within 3 to 5 years
• Potential to create significant economic impact on the local community
USF Research Park update
http://www.research.usf.edu/absolutenm/templates/newro.asp?articleid=182&zoneid=26
USF Research Park Grows
By Rebecca Puig
Friday, March 12, 2004 - Miles of galvanized fencing surround a group of earthmovers at the University of South Florida’s Research Park. Their roars signal the start of two new buildings being constructed to house high-tech research partnerships.
A projected budget of $40 million dollars has been slated for the construction of the two buildings. Funding will come from a number of sources, the most prominent being the USF Foundation’s annual contribution to research.
Another portion of the funding will be from the sale of bonds, which are guaranteed against the Facilities and Administrative fees (F&A, a.k.a. overhead, indirect costs), which are factored into the cost of each grant and are earmarked to support research infrastructure.
Congressman Bill Young’s Homeland Security directive will provide $12 million for the relocation and expansion of the Center for Biological Defense into its new home in the new Interdisciplinary Research building.
Additional funding is expected to come from state and federal grants and rental fees from tenants.
The Business Partnerships Building will be the first of two to be constructed. It will offer over 100,000 square feet of state-of-the-art office space in addition to wet and dry labs (a combination not often found in a typical corporate park). The Partnerships Building will provide a bridge between USF and the community to apply innovations and research discoveries developed at USF.
The Business Partnerships Building will also be home to the Tampa Bay Technology Incubator. The list of companies going into the incubator reads like a “who’s who” of research technology: BioMedTech Laboratories, DNAPrint Genomics, Imigene, Nanopham Technologies, Nanobac Pharmaceuticals, Saneron CCEL Therapeutics, Transgenex Therapeutics, Medegy, and Modelithics.
The tenants will have access to USF Connect, a program designed to tie together the elements of economic development at USF. It will provide a single point of contact for businesses and entrepreneurial communities to access many of the resources necessary for success: intellectual property, management expertise, capital partners, and support services.
In addition to USF Connect, the tenants will be able to benefit from USF’s new commitment to research. This year alone the university brought in over $250 million for research, up 23% from last year. The start of the new buildings is just one of the many examples stemming from USF’s pledge to become a major player in the national research arena.
The latest issue of The Top American Research Universities, an annual report developed by the TheCenter, an enterprise at the University of Florida that offers analysis and data useful for understanding research performance, ranked USF 43rd in the nation among public research universities for total research funding.
Data collected for fiscal years 1997-2000 by the National Science Foundation shows USF ranked 75th out of the 641 institutions surveyed in total Research and Development Expenditures; 104th out of 1,515 institutions in science and engineering obligations; and 54th out of 606 institutions surveyed in total number of graduate students enrolled full-time.
The Center for Urban Transportation Research (CUTR) bubbled up among the top 10 centers in a recent national survey by the Urban Transportation Monitor, and USF’s Life Sciences Entrepreneurship program beat out Stanford University for the number one specialty entrepreneurship program in the country according to the United States Association for Small Business and Entrepreneurship (USASBE).
Among 71 national research universities surveyed, USF ranked fourth in the number of inventions licensed to start-up companies and first among universities with similar profiles.
Technology startup companies could not ask for a better location or partnership along the Florida High Technology Corridor than the University of South Florida.
OT Spook, no they were private emails and the correspondents, although aware that I am a DNAP shareholder, would probably not appreciate my posting their views in this forum.
For the more technically minded, I found a link to the full text for the following article:
Matsuzaki H, Loi H, Dong S, Tsai YY, Fang J, Law J, Di X, Liu WM, Yang G, Liu G, Huang J, Kennedy GC, Ryder TB, Marcus GA, Walsh PS, Shriver MD, Puck JM, Jones KW, Mei R. Parallel Genotyping of Over 10,000 SNPs Using a One-Primer Assay on a High-Density Oligonucleotide Array. Genome Res. 2004 Mar;14(3):414-25.
http://egweb.bcgsc.ca/journal_club/2003_2004/pdfs/journal_club_040322.pdf
PSU Liberal Arts Magazine
Here is an article in the March 2004 issue of the above. Nothing new, but a nice summary of Mark Shriver's work.
http://alumni.la.psu.edu/stories/ezine/issue18/issue18.htm
WHAT IS AN ANCESTRY INFORMATIVE MARKER?
Geneticist Mark Shriver, assistant professor of biological anthropology, performs what might be thought of as DNA macro-analysis. Shriver’s technique considers DNA samples from large numbers of people, looking at the broadest trends and “markers” (specific positions where there are sequence differences) which have taken thousands of years to develop.
“Much of the human genome is very similar,” Shriver says. “So if you analyze several samples at once, and most of it looks very similar, those places that have differences show up dramatically.”
Such markers can often correlate with disease, but can just as often signify a difference in an expressed trait, or be of no consequence whatsoever. An expressed trait, or “phenotype,” might be an aspect of physical appearance, the likelihood of contracting a disease, or any result of a genetic code as it manifests itself in an individual and is effected by environment.
Scientists agree that the human genome looks the way it does today due to its evolution over thousands of years of natural selection, mutation, migration, and random drift (for a definition of random drift, click here). People interact and reproduce, and certain traits endure in the species while others disappear.
But because large groups of individuals were isolated by various factors—mainly geological barriers—off and on over the history of human evolution, there are some rare markers that have persevered in their gene pools. The “allele frequencies” (click here for a definition) within the markers reveal the populations’ geographic origins. Generally, allele frequencies are quite similar across all human populations, reflecting our very recent common origin.
Shriver’s work, termed admixture mapping, looks at the changes in genetic profiles that have resulted as large populations came in contact with one another. For instance, when people of West Africa—which includes several different groups—came in contact with groups comprised of what we think of today as Europeans and American Indians, resulting offspring carried markers from each group.
What does such work tell us? Shriver's lab works on applications of population genetics to questions of human origins and human evolution. Which groups moved where and when? How did they interact, genetically? Shriver focuses particularly on normal and disease phenotypes that may have been subject to recent (last several thousand years) active natural selection. These phenotypes include chronic diseases such as obesity, diabetes, and hypertension, and normal variation in common traits, namely skin and hair pigmentation, tooth features, and stature.
One interesting point Shriver makes resulting from his work is that there is no typological basis for race. That is, no common characteristics allow for biological classification of race. He explains, “Human populations are too closely related to be considered subspecies. The surface appearance differences are too superficial to constitute such categorization. There are no ‘pure’ human stocks and never were.”
Rather, Shriver points out that race as generally understood and as used in biomedical research refers to cultural, social, and biological features of population groups. The designation suggests greater human variation than actually exists biologically. Although much genetic variation is shared among all human populations, only about 5 percent of such markers can be considered “Ancestry Informative Markers.”The results suggest what is supported by the movement of people over time: ancestry is a tricky matter.
“It is simplistic to equate skin color and race,” Shriver says. “There are both dark and light skinned populations in most parts of the world and extensive variation in pigmentation within most regions.”
Even so, because Shriver’s work has pinpointed ancestry informative markers, or AIMs, the science can be used for things other than population genetics. For instance, Shriver’s research attracted national press coverage in June 2003, when the New York Times reported that his techniques had been used to alter a police investigation, revealing a murder suspect to be a black man, rather than a white man, as profilers had deduced.
The technique is also being used to allow individuals to learn their ancestry mix. A consulting business employs the technique to provide the test. People who are thought of culturally as “white,” through such a test might find, for instance, that their AIMs reveal them to be 80 percent European ancestry, 12 percent West African, and 8 percent American Indian.
Shriver points out that many Americans will find their ancestry to be comprised of many different peoples, with roots around the world, and that ancestry suggests much more complexity than do cultural labels such as white or black or Native American.
spook, when (if) you get permission to post the missive in question I will be interested to see the details. I have had several email exchanges with RootsWeb stalwarts myself.
Personally I liked the one where Tony Frudakis asked the malcontent concerned whether he would like to cancel his outstanding Ancestry order given his continued criticism on RootsWeb. I don't remember seeing a repy to that post...
This is a selection of quotes from malcontents on RootsWeb. Why don't you post some of the messages from Tony Frudakis refuting the claims?
bag8ger, not to mention the National Center for Forensic Science, who also participated with the San Diego Police Department Crime Lab in the DNA Witness validation studies.
This looks to me like typical change resistance and reluctance to adopt new technology. The good old status quo. You need people with a bit of vision to champion change in organizations lile the typical Police Department.
Here are some patents that are visible at the patent office:
United States Patent Application 20040048265
Cohen, Daniel et al. March 11, 2004
Obesity associated biallelic marker maps
Abstract
The present invention relates to genomic maps comprising biallelic markers, new biallelic markers, and methods of using biallelic markers. Primers hybridizing to regions flanking these biallelic markers are also provided. This invention provides polynucleotides and methods suitable for genotyping a nucleic acid containing sample for one or more biallelic markers of the invention. Further, the invention provides a number of methods utilizing the biallelic markers of the invention including methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype.
United States Patent Application 20040038231
Blumenfeld, Marta et al. February 26, 2004
Biallelic markers related to genes involved in drug metabolism
Abstract
The invention provides polynucleotides including biallelic markers derived from genes involved in the biotransformation of xenobiotics such as drugs and from genomic regions flanking those genes. Primers hybridizing to regions flanking these biallelic markers are also provided. This invention also provides polynucleotides and methods suitable for genotyping a nucleic acid containing sample for one or more biallelic markers of the invention. Further, the invention provides methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype.
United States Patent Application 20040023860
Yen, Frances et al. February 5, 2004
Methods and compositions for inhibiting neoplastic cell growth
Abstract
The invention provides the genomic sequence of GSSP-2, GSSP-2 cDNAs and GSSP-2 polypeptides. Further the invention provides polynucleotides including biallelic markers derived from the GSSP-2 gene and from genomic regions flanking the gene. This invention also provides polynucleotides and methods suitable for genotyping a nucleic acid molecule containing sample for one or more biallelic markers of the invention. Further, the invention provides methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype. The invention also concerns methods and compositions for killing neoplastic cells or inhibiting neoplastic cell growth. In particular, the present invention concerns cell proliferation arresting/inhibiting and apoptosis/necrosis inducing compositions and methods for the treatment of tumors. The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides.
(This one is formally assigned to Genset)
United States Patent Application 20040005584
Cohen, Daniel et al. January 8, 2004
Biallelic markers for use in constructing a high density disequilibrium map of the human genome
Abstract
The present invention relates to genomic maps comprising biallelic markers, new biallelic markers, and methods of using biallelic markers. Primers hybridizing to regions flanking these biallelic markers are also provided. This invention provides polynucleotides and methods suitable for genotyping a nucleic acid containing sample for one or more biallelic markers of the invention. Further, the invention provides a number of methods utilizing the biallelic markers of the invention including methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype.
United States Patent Application 20030228582
Blumenfeld, Marta et al. December 11, 2003
Biallelic markers derived from genomic regions carrying genes involved in arachidonic acid metabolism
Abstract
The invention provides polynucleotides including biallelic markers derived from genes involved in arachidonic acid metabolism and from genomic regions flanking those genes. Primers hybridizing to regions flanking these biallelic markers are also provided. This invention also provides polynucleotides and methods suitable for genotyping a nucleic acid containing sample for one or more biallelic markers of the invention. Further, the invention provides methods to detect a statistical correlation between a biallelic marker allele and a phenotype and/or between a biallelic marker haplotype and a phenotype.
All of the people associated with these patents are or were at Genset in Paris (acquired by Serono last year).
Molecular Genetics of Pigmentation
I would keep an eye on this guy as well (Rick Sturm):
http://www.imb.uq.edu.au/index.html?id=11690
Duffy DL, Box NF, Chen W, Palmer JS, Montgomery GW, James MR, Hayward NK, Martin NG, Sturm RA. Interactive effects of MC1R and OCA2 on melanoma risk phenotypes. Hum Mol Genet. 2004 Feb 15;13(4):447-61. Epub 2004 Jan 06.
Queensland Insititute of Medical Research, Brisbane, Australia.
The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.
Human trait research at CRC
http://diagnosticscrc.org/research/programs.html
Project 3: Single nucleotide polymorphism (SNP) detection technologies
Leaders: A. van Daal and P. Morris
Objectives To develop simple, cost effective, high throughput SNP detection technologies designed for immediate market uptake, making use of currently identified SNPs. Our objective is to develop SNP technologies that meet the needs of medical diagnostics rather than pharmacogenomics SNP studies, i.e. we will develop technologies to detect small numbers of SNPs in a large number of samples at low cost per sample. To ensure these testing formats are designed for immediate market uptake, they will be compatible with the expertise and instrumentation levels seen in the current Australian private pathology industry. These technologies initially will be applied in microplate-based, ELISA-like DNA assays. We aim ultimately to develop homogeneous end-point assays to meet the longer-term needs of the diagnostics industry. We also will generate a profile of useful SNPs involved in physical traits for development of forensic identification assays.
Background The present market for genetic analysis is limited to a small number of genetic diseases and some forensic and paternity applications in a small number of highly specialised laboratories. In order to accommodate the anticipated explosion of informative SNP markers it is necessary to develop approaches that allow the simple, rapid, high-throughput, inexpensive analysis of SNPs. Current gel-based methods cannot be used for high throughput applications as they are complex, labour intensive and expensive.
Some time ago homogeneous, closed-tube assays such as the “Taqman” system emerged as a possible solution to some of these problems, despite the high cost of instrumentation and consumables. Most of the SNP detection methods being developed elsewhere to meet the pharmacogenomics needs of large pharmaceutical companies are expensive, “high tech” solutions designed to meet the needs of gene association studies, i.e. they can detect very large numbers of SNPs in limited numbers of trial participants at a low cost per SNP. The needs of medical diagnostics are different, i.e. the detection of small numbers of SNPs in a large number of samples at low cost per sample.
It is envisaged that technologies from the former CRC for Diagnostic Technologies' existing IP portfolio (SPA, SNAAC, RCA, etc.) will be integrated into testing formats where appropriate and opportunities to develop new IP in the form of novel diagnostic technologies and new SNP targets will be exploited. The most appropriate technology required to construct a diagnostic assay will be selected to solve the individual diagnostic problem. With significant experience in DNA forensics and excellent access to samples, CDx is in an strong position to identify new forensically useful SNP targets and this project will provide SNP detection technologies for this purpose.
We have looked at this program before:
http://www.investorshub.com/boards/read_msg.asp?message_id=2081647
This is new though:
http://diagnosticscrc.org/business/patents.html
Provisional Phase Patents
An Assay (Human Physical Trait SNPs)
Application No 2003904687
Strangely enough this patent isn't visible at the patent office either...
DNAP in the LA Times
http://www.latimes.com/news/local/state/la-me-onthelaw12mar12,1,2394047.story?coll=la-news-state
March 12, 2004
Firm Seeks to Win Over Police to DNA-Based Strategy
Florida company says its technology can aid in narrowing searches for suspects. But some experts doubt accuracy of racial prediction.
By Jill Leovy, Times Staff Writer
Zach Gaskin might be called a connoisseur of genotypes.
At airports or company meetings, he studies faces, eyes, complexions. And sometimes, he just can't resist.
"You look like an interesting mix," he'll say to strangers. "Can we test your DNA?"
Those who are not too taken aback may become new entries in a growing catalog of DNA types being collected by Gaskin's employer. The enterprise, Gaskin acknowledged, is sometimes perceived as a potentially offensive application of genetic science to crime-fighting. But he contends it should be viewed as just the contrary: a counterweight to unfounded notions of racial differences.
Gaskin, technical director for a Sarasota, Fla., company called DNAPrint genomics Inc., was one of a handful of vendors hawking wares at a recent California Homicide Investigators Assn. conference held by the Los Angeles Police Department in Universal City, and the only private contractor to be deemed worthy of a lengthy presentation before the whole conference, which drew about 650 detectives from around the state.
It wasn't the company's first foray into L.A., however. Gaskin said he had been seeking the LAPD's business for some time — so far drawing interest, but no commitments.
In the year DNAPrint has been providing forensic services to police nationwide, it has aided in about 25 investigations, he said — only two of which have resulted in arrests. In one high-profile case, that of a Louisiana serial killer, a task force that included Baton Rouge police used DNAPrint to conclude that their suspect was probably not a white man, but a black man.
LAPD Det. Dennis Kilcoyne, one of the conference organizers, said he had sought out DNAPrint simply because he was intrigued by potential future uses of new DNA technology.
"They say this technology is developing so fast that, just around the corner, we will have a speck of something from a crime scene, and DNA will tell us hair and eye color," he said. "The stuff they are talking about is very 'Star Wars.' … We can't comprehend what's down the road."
Some experts, however, doubt DNA tests' ability to predict racial identity, because people of all colors tend to have mixed ancestry. "I would be surprised" if the test were very accurate, said Wayne Grody, director of the DNA Diagnostic Laboratory at UCLA.
Scientists have found a few examples of particular genetic mutations passed through generations in populations with little history of mixing outside their group, he said, but such findings could more accurately be said to mark "accidents of history" than to describe what many people think of as race.
Race, agreed Jeanette Papp, a UCLA professor of human genetics, "is a social construct, not a biological reality."
There are more differences "between baboons in adjacent valleys in Africa than people from Sweden and Africa," she said.
The little information such tests could yield, she added, might not be worth "a big price in bad PR." And some LAPD detectives said DNAPrint's findings seemed too vague and general to be of much help.
But 77th Street Division Det. Daniel Myers was interested: "In cases where we have DNA but don't know a suspect, it might be nice to have a profile," he said.
A publicly traded start-up that has never posted a profit, DNAPrint is now sending its representatives west in the hope of picking up more contracts from California law enforcement agencies, Gaskin said.
DNAPrint's investigative branch, called DNAWitness, claims to be able to help investigators narrow searches for suspects, or for unidentified victims, by comparing information from their DNA with data from sample groups tested around the world. The company breaks down information from individuals' DNA into percentages matching that of sample groups of sub-Saharan Africans, Native Americans, East Asians and Indo-Europeans.
Most people's DNA is a mix of two or more groupings. But proportions vary, and it is the variation DNAPrint uses to predict ethnic identification. Gaskin acknowledged that the comparisons are based on smaller sample groups than the company would like, but he argued that its growing database would improve the service with time.
A blind test of the technology on homicide detectives at the conference last week produced mostly accurate findings, though some were quite broad — South Asian, Native American or Caucasian, for example, was one finding. The test is better at eliminating possibilities than pinpointing race, Gaskin said.
But what the test most vividly demonstrated was the variety of ancestry that hides behind loose generalities of race. A quarter of the DNA of a detective who identified herself as African American tested as European. A seventh of that of a detective who identified himself as white tested as African.
That's typical, Gaskin said. People who look white commonly have nonwhite DNA. In the company's tests, African ancestry has been especially likely to show up in people of Scandinavian heritage, for example. And Asian ancestry is especially common in those of German and East European heritage, he said.
African Americans usually prove to have significant shares of DNA that match European or Native American samples, and Latinos, he said, are an exceptionally unpredictable mix.
In general, Gaskin avoids using the definitive language that commonly characterizes race in everyday speech. He does not talk of people's race, but rather, their mix. He does not refer to people's "being" black or white, but rather, as having genetic profiles consistent with those of surveyed individuals who identify themselves as one or the other.
What race you call yourself, Gaskin said, may be predicted to some degree by your ancestry. And this, in turn, may yield clues as to where you might live, your background, your culture — all variables that might somehow be relevant to solving a crime.
But police officials said they would require an independent evaluation of the company's claims before considering the service.
"We are always interested in new technologies," said Steve Johnson, administrator of the LAPD's Scientific Investigation Division. "But obviously, a lot more work needs to be done before using taxpayers' funds to fund that kind of work."
bag8ger, yes disease prevention and disease management are a focus, which shows how forward thinking Malaysia is in some ways (in others it is not lol). I did see Seattle's well thought-out RB post. There is still that underlying problem with the HMOs themselves not being interested in any approach that does not demonstrate a return on investment in under a year. The St. Louis Regional Commerce & Growth Association might also allow GMED to offer their regime to smaller businesses that do not have medical insurance coverage.
Something to think about in terms of potential revenue opportunities is the Malaysian Multimedia Super Corridor (MSC) TeleHealth Flagship Application.
http://www.msc.com.my/msc/flagship.asp#telehealth
The Telehealth initiative aims to keep people in the ‘wellness’ paradigm, through the seamless availability of health information and virtual health services thus transforming the way healthcare services are delivered and accessed. Definition of Telehealth is a multimedia network linking all players to provide products and services in health care.
The four Telehealth Flagship Application pilot projects are :
1. Teleconsultation (TC)
2. Mass Customised / Personalised Health Information and Education (MCPHIE)
3. Lifetime Health Plan (LHP)
4. Continuing Medical Education (CME)
http://www.telehealth.com.my/english/cme.html
Continuing Medical Education (CME) is defined as educational and learning activities which serve to maintain, develop/increase the knowledge, skills, professional performance and relationship that a healthcare provider uses to provide services for patients, the public and for his/her own profession.
In short, the purpose of CME is to drive the medical and health practice.
The CME system developed will be integrated into and interfaced with the other applications within the Telehealth framework, namely, Lifetime Health Plan (LHP), Mass Customised/Personalised Health Information and Education (MCPHIE) and Teleconsultation.
The three services provided under CME are: Electronic Courses Educational courses offered via the Internet and other channels of delivery.
The two main types of electronic courses are:
Modular Distance Learning (MDL)
Refers to modular educational programs that can be tied to the issuance of the annual practicing certificate for medical practitioners and for other categories of allied health staff. We will offer modular courses in accordance with priority health topics.
Formal Distance Learning (FDL)
A structured educational programs run by accredited educational and professional institutions and organisations that will result in the award of paper qualifications, with focus on facilitating delivery of courses run by the government and universities. We will also provide online materials to assist the skill-based components of the courses through simulation or audio-visual aids.
Creation of Online Professional Community Service
We will offer an application for the creation of a virtual community, which ultimately will make the CME programs and web site dynamically evolving entities. These services will ensure continuous use by the virtual community members with their regular feedbacks. The services will offer a variety of collaborative tools, namely e-mail, white-boarding, online professional discussions, newsgroup, audio and video conferencing, application sharing, file transfer and web site hosting.
Virtual Resources
Virtual Resources refer to sources of information located in cyberspace accessible with the aid of web-based technologies. Our services include gateways to real libraries, virtual library links to other library services, medical databases, online biomedical journals and other CME web sites. We will provide other value-added services such as creation of local medical knowledge-based databases. The Virtual Resources shall form a "one-stop center" where quality health information covering a wide scope of needs and interests (academic or otherwise) beneficial to the health and medical professionals, are made available.
http://www.phenomed.net/news.htm
Phenomed's U.S. Partner, GenoMed Inc., Offers Web-Based Medical Education Course on Genomics For Physicians
Web-Based Course to Enhance Awareness of Genomic Medicine
KUALA LUMPUR, Malaysia – February 27, 2004 – PhenoMed, a development-stage disease management and medical-pharmaceutical therapeutic company, today announced its U.S. partner, GenoMed Inc. (OTC: GMED), has formally launched a Web-based course on genomics for practicing physicians.
Information about the course is available at:
http://www.cme-webcredits.org/tests/genome
Although the course was designed to service the 650,000 physicians in the U.S. who require continuing medical education (CME) to keep their medical license active, the online course can be taken by anyone interested in this field. As Ezehan Kamaluddin, Phenomed's COO commented, "those physicians joining Phenomed's disease management network will certainly be encouraged to draw upon this important resource. This course will also be worthwhile for those physicians participating in our clinical trials research."
"There is a huge need for this type of Internet education. Physicians need to learn about genomics, and they need to do so in the most time- and cost-effective manner possible. Physicians can earn two years' worth of CME credit in their spare time, without having to leave their busy practices to attend a conference. GenoMed will serve as a for-profit postgraduate medical university for these physicians," said David W. Moskowitz, M.D., GenoMed Chairman, CEO and Chief Medical Officer. "We have been developing this course since September 2002 and we are delighted that it is now being launched."
GenoMed has partnered with Health Communication Research Institute, Inc. (http://www.hcri.com), a non-profit company which is a pioneer in Web-based education for physicians.
Now the only thing that is missing is some sort of formal tie-up between Malaysia's CME Telehealth Flagship Application pilot project and the Health Communication Research Institute so that this course can be offered as part of the former.
Incidentally, a good source of general information about Telemedicine is the Telemedicine Information Exchange:
http://tie.telemed.org/
This is an interesting development. There is of course nothing in the press release per se which states that any large St. Louis employer is going to be signing up for GMED's Clinical Outcomes Improvement Program; however reading between the lines Dave Moskowitz clearly sees this as an opportunity. Personally I think it is important that GMED are part of the Regional Commerce & Growth Association, as this shows that they are to some extent joining the mainstream. Now all we need is for one of the employers to break ranks and the rest of the sheep will follow...
Some facts about the DNAP/GMED Genotyping Agreement
The DNAP/GMED Genotyping Agreement is an exhibit attached to the 10K filed on April 9, 2002:
http://www.sec.gov/Archives/edgar/data/1127354/000107087602000030/genotypingagmt1015.htm
The main provisions of this agreement were as follows:
GMED agreed to place at DNAP certain equipment (mainly the Orchid UHT genotyping platform system) to facilitate increased genotyping throughput by DNAP. DNAP was to provide GMED with at least 3 Million genotypes during the first year of the, GMED was to provide DNAP with DNA specimens for genotyping. GMED was to make monthly payments to DNAP calculated at the rate of 40 cents per genotype.
If GMED was to realize a NET profit that exceeded US$10 million which was "directly or indirectly enabled by compositions of matter produced under the terms" of the agreement then GMED would pay DNAP a royalty of 5% on these realized NET profits.
During the term of the Agreement, DNAP was allowed to use GMED's equipment for its own internal R&D, and for other contract genotyping with GMED approval. For the latter DNAP and GMED were to share total NET profits at a ratio of 3:1 to reflect their relative contributions.
The minimum term of the agreement was 2 years, after which it was to continue indefinitely, but could be terminated by either party on a material breach by the other (the breaching party being allowed thirty (30) days to cure such breach).
On discontinuation of the agreement GMED would pay any outstanding debts to DNAP and DNAP would return GMED's equipment. Normal clauses like Force Majeure were included (neither party is liable for any failure of delay caused by events outside its control).
From the January 2003 DNAP shareholder newsletter:
"What happened to GMED revenue? We have received part of this revenue but nowhere near what GMED agreed to provide. The contract is not yet up, but it is a certainty that GMED will be in default of this agreement by the time it is up. Their problems are the same as everyone’s – they have difficulty-raising funding. Do not forget that DNAPrint got the use of a faster cheaper machine that cost 200K as part of this deal, so we have already benefited from that partnership. We have received probably another 100K from them for early work orders but this is a far cry from $1.6M and there is little we can do about it but sue them. If you look at their financial statements, I think you would see that this would make little sense."
So, where does that leave us? There are a number of unresolved issues and open questions. I think in practice that GMED were in default of the agreement by the time the term expired. The effective date of the agreement was January 15, 2002 so the initial two year term has expired and we can assume that is has not been extended. Some of the clauses survive expiration of the agreement though, and so there are continuing liabilities under the agreement for both parties.
GMED were clearly in breach of the agreement, but we do not know whether they were formally given 30 days to remedy this, failed to do so and hence the agreement was formally terminated by DNAP. Similarly we do not know if GMED could have, or did, claim no joy under the force majeure provision.
Who is the current owner of the Orchid equipment purchased by GMED? Technically I think GMED still own it. Does this mean that GMED could now ask for it back if they wanted to undertake their own genotyping? If they could why haven't they?
Could DNAP at this stage sue GMED (given that they now will have revenue)? This does not make much sense to my mind, even if DNAP could sue GMED.
Will the agreement be resurrected? I seem to remember Dave Moskowitz saying at some point that he potentially had access to alternate genotyping capabilities at reduced cost. If it was resurrected would DNAP reduce the cost? According to their website they "offer genotyping rates as low as $0.47 (in volume) per genotype" which is still more than the rate contained in the agreement.
Would any future GMED revenues be covered by the net profit clause in the agreement and would DNAP actually be able to claim their 5% royalty on these profits? Presumably any revenues that were or would be related to the circa US$100K genotyping that was undertaken would be covered in this context. I do not think therefore in practice that DNAP will see any such royalties unless the agreement is resurrected.
Does DNAP still need GMED's approval for third party genotyping work? Would they still be required to split revenues in the 3:1 ratio with GMED for any such work? Technically the answer to both of these questions is yes.
So I think as things stand that the Orchid machine is the property of GMED. DNAP cannot use it for third party genotyping without GMED's permission (and then they share such revenues), and DNAP does not stand to benefit from any royalties related to GMED revenues. It will be interesting to see the pending 10K's from both companies to see if there is any mention of the agreement and where, in practice, we go from here.
You mean this Murray Brilliant, who increasingly works with Mike Hammer:
Yi Z, Garrison N, Cohen-Barak O, Karafet TM, King RA, Erickson RP, Hammer MF, Brilliant MH. A 122.5-kilobase deletion of the P gene underlies the high prevalence of oculocutaneous albinism type 2 in the Navajo population. Am J Hum Genet. 2003 Jan;72(1):62-72. Epub 2002 Dec 05.
Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Oculocutaneous albinism (OCA) is a genetically heterogeneous disorder. There are four known types of OCA: OCA1-OCA4. The clinical manifestations of all types of OCA include skin and hair hypopigmentation and visual impairment. Although there are a few documented observations of high frequency of albinism among Native Americans, including the Hopi, Zuni, Kuna, Jemez, Laguna, San Juan, and Navajo, no causative molecular defect has been previously reported. In the present study, we show that albinism in one Native American population, the Navajo, is caused by a LINE-mediated 122.5-kilobase deletion of the P gene, thus demonstrating that albinism in this population is OCA2. This deletion appears to be Navajo specific, because this allele was not detected in 34 other individuals with albinism who listed other Native American origins, nor has it been reported in any other ethnic group. The molecular characterization of this deletion allele allowed us to design a three-primer polymerase chain reaction system to estimate the carrier frequency in the Navajo population by screening 134 unrelated normally pigmented Navajos. The carrier frequency was found to be approximately 4.5%. The estimated prevalence of OCA2 in Navajos is between approximately 1 per 1,500 and 1 per 2,000. We further estimate that this mutation originated 400-1,000 years ago from a single founder.
http://www.familytreedna.com/about.html
We saw this recently through another of Mark Shriver's collaborators...
The uses and limitations of DNA based ancestry tests for Native Americans
http://www.tracegenetics.com/nativeamericandna.pdf
III. The autosomal (genome-wide) test
The autosomal test traces the ancestry of your genome (maternal and paternal) and provides percentage ancestry in broad geographic and linguistic groupings (not races), namely Sub-Saharan African, East Asian, European (namely, the Caucasoids, the diaspora of which correspond roughly to the distribution of individuals part of a language family that spreads from Western Europe to Northern India), and Native American. It should be noted that the current test offered has from 3-12% reported error rate (depending on the type of interbreeding, see Table 2 below), meaning that any ancestry in these groupings that is below 3-12% (depending on the groups) are not certain at the 95% confidence level (i.e. they could be inaccurately reported). Conversely, very low levels (<3%) of ancestry may not be detected. The test operates by screening approximately 180 genetic markers that show large frequency differences among the four population samples comprising the database. The inference of percentage ancestry is made from a statistical analysis of the 180 informative markers.
Table 2. Based on simulations, the minimum percentage ancestry required for accurate reporting in individuals of two ancestral backgrounds (unpublished data Frudakis and Shriver).
AFR EUR EAS NAM
Africans < 3.0% 7% 5% <3%
Europeans 3.50% < 3.0% 9% 10%
East Asians < 3.0% 8% < 3.0% 12.50%
Native American < 3.0% 7.50% 11.50% < 3.0%
The above table shows that greater than or equal to 10% Native American ancestry is required for an individual of polarized (i.e. mainly) European ancestry to conclude with 95% confidence that there is Native American ancestry. A greater than or equal to 12.5% Native American ancestry is needed for an individual of Native American and East Asian ancestry to conclude with accuracy that there is Native American ancestry. The values required to conclude Native American ancestry with 90% certainty are about 2/3rds those shown in Table 2.
Accuracy and Sampling Error
The individuals originally studied to determine Native American ancestry markers in this test are all from Southwest North America. Therefore, individuals with Native American ancestry from this region will likely be identified. However, Native American ancestry from other regions of North America may not be accurately identified. Unpublished research (Frudakis and Shriver) has shown that documented and relatively homogeneous American Indians from the United States reliably type with majority Native American ancestry using this test, and other research is ongoing to further define the sensitivity and accuracy limits in this subgroup of Native Americans.
The future of DNA testing to determine Native American Ancestry
Through haplotype analysis, DNA tests are already quite reliable in determining Native American ancestry along the direct maternal and paternal lines. Currently, the autosomal (genome-wide) test is fairly accurate at identifying individuals with a high percentage of Native American ancestry from Southwest North America, and unpublished data suggests that persons with Native American ancestry from outside of the Southwest also type as of mainly Native American ancestry using the Southwest group as a “calibration” group, but the sensitivity and accuracy in this group has yet to be established and could be lower for Native American groups distantly related to those in the Southwest. We can expect additional haplotypes that are informative about geographic and tribal ancestry within North America to be developed through advanced analyses that screen larger portions of the mitochondrial genome and the Y chromosome. For mtDNA only a small segment (approximately 2%) of the mitochondrial genome is sequenced to determine ancestry. Fortunately technological advances now allow for economical sequencing of the entire mitochondrial genome and researchers are already doing this for samples in the Americas (Bandelt et al. 2003). The number of informative markers available for analysis of ancestry based on the Y chromosome has increased substantially in the past few years (Zegura et al. 2003). With an appropriate sampling scheme, there is still a large potential for identifying Y chromosome markers that are informative about geographic and tribal ancestry within North America to be developed. Additional data for identifying autosomal markers that are informative about Native American ancestry have recently been published (Rosenberg et al. 2003, Collins-Schramm et al. 2003). With this data and an appropriate sampling scheme for the collection of samples, more accurate autosomal tests for determining and quantifying Native American ancestry will likely be available in the near future. The success of increasing the informativeness and accuracy of DNA based ancestry tests for Native Americans is highly dependent upon additional sampling of Native American individuals, which is contingent upon mutually beneficial relationships between private testing companies, universities, and Native American communities. Many Native American groups are understandably leery of the motives of private companies and government or university researchers. However a recent survey investigating the attitudes of Native American groups about genetic testing indicate that many Native American individuals do not oppose genetic research and believe they can benefit from it (Schroeder et al. 2004). To ensure that proper safeguards are in place to adequately protect Native American participants from the risks of genetic research, Native American communities would benefit from working with university researchers who are required to participate in human subjects protection protocols before proceeding with a project. Fortunately, the horizon looks bright for collaboration between Native American communities and university researchers on genetic research. Funding to initiate such collaborations is available through the National Human Genome Research Institute (NHGRI) and articles addressing issues of the best ways to proceed with such collaborations are becoming more frequent in the academic literature. Certain Native American communities are also taking a pro-active role in these collaborations and the direction and goals of research projects are being determined by Native American communities as well as researchers. Finally, it is up to the private DNA testing company to ensure that they are presenting the information about these diagnostic tests as accurately as possible. Due to the rapidly changing landscape of DNA based ancestry tests, private companies that are closely allied with university and academic research will likely be the companies with the best interpretation of the results from DNA based ancestry tests for Native Americans.
This is some of the recent research referred to above:
Collins-Schramm HE, Chima B, Morii T, Wah K, Figueroa Y, Criswell LA, Hanson RL, Knowler WC, Silva G, Belmont JW, Seldin MF. Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians. Hum Genet. 2004 Feb;114(3):263-71. Epub 2003 Nov 20.
Rowe Program in Human Genetics, Department of Biological Chemistry, University of California at Davis, One Shields Avenue, Davis, CA 95616-8669, USA.
Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.
The uses and limitations of DNA based ancestry tests for Native Americans
http://www.tracegenetics.com/nativeamericandna.pdf
III. The autosomal (genome-wide) test
The autosomal test traces the ancestry of your genome (maternal and paternal) and provides percentage ancestry in broad geographic and linguistic groupings (not races), namely Sub-Saharan African, East Asian, European (namely, the Caucasoids, the diaspora of which correspond roughly to the distribution of individuals part of a language family that spreads from Western Europe to Northern India), and Native American. It should be noted that the current test offered has from 3-12% reported error rate (depending on the type of interbreeding, see Table 2 below), meaning that any ancestry in these groupings that is below 3-12% (depending on the groups) are not certain at the 95% confidence level (i.e. they could be inaccurately reported). Conversely, very low levels (<3%) of ancestry may not be detected. The test operates by screening approximately 180 genetic markers that show large frequency differences among the four population samples comprising the database. The inference of percentage ancestry is made from a statistical analysis of the 180 informative markers.
Table 2. Based on simulations, the minimum percentage ancestry required for accurate reporting in individuals of two ancestral backgrounds (unpublished data Frudakis and Shriver).
AFR EUR EAS NAM
Africans < 3.0% 7% 5% <3%
Europeans 3.50% < 3.0% 9% 10%
East Asians < 3.0% 8% < 3.0% 12.50%
Native American < 3.0% 7.50% 11.50% < 3.0%
The above table shows that greater than or equal to 10% Native American ancestry is required for an individual of polarized (i.e. mainly) European ancestry to conclude with 95% confidence that there is Native American ancestry. A greater than or equal to 12.5% Native American ancestry is needed for an individual of Native American and East Asian ancestry to conclude with accuracy that there is Native American ancestry. The values required to conclude Native American ancestry with 90% certainty are about 2/3rds those shown in Table 2.
Accuracy and Sampling Error
The individuals originally studied to determine Native American ancestry markers in this test are all from Southwest North America. Therefore, individuals with Native American ancestry from this region will likely be identified. However, Native American ancestry from other regions of North America may not be accurately identified. Unpublished research (Frudakis and Shriver) has shown that documented and relatively homogeneous American Indians from the United States reliably type with majority Native American ancestry using this test, and other research is ongoing to further define the sensitivity and accuracy limits in this subgroup of Native Americans.
The future of DNA testing to determine Native American Ancestry
Through haplotype analysis, DNA tests are already quite reliable in determining Native American ancestry along the direct maternal and paternal lines. Currently, the autosomal (genome-wide) test is fairly accurate at identifying individuals with a high percentage of Native American ancestry from Southwest North America, and unpublished data suggests that persons with Native American ancestry from outside of the Southwest also type as of mainly Native American ancestry using the Southwest group as a “calibration” group, but the sensitivity and accuracy in this group has yet to be established and could be lower for Native American groups distantly related to those in the Southwest. We can expect additional haplotypes that are informative about geographic and tribal ancestry within North America to be developed through advanced analyses that screen larger portions of the mitochondrial genome and the Y chromosome. For mtDNA only a small segment (approximately 2%) of the mitochondrial genome is sequenced to determine ancestry. Fortunately technological advances now allow for economical sequencing of the entire mitochondrial genome and researchers are already doing this for samples in the Americas (Bandelt et al. 2003). The number of informative markers available for analysis of ancestry based on the Y chromosome has increased substantially in the past few years (Zegura et al. 2003). With an appropriate sampling scheme, there is still a large potential for identifying Y chromosome markers that are informative about geographic and tribal ancestry within North America to be developed. Additional data for identifying autosomal markers that are informative about Native American ancestry have recently been published (Rosenberg et al. 2003, Collins-Schramm et al. 2003). With this data and an appropriate sampling scheme for the collection of samples, more accurate autosomal tests for determining and quantifying Native American ancestry will likely be available in the near future. The success of increasing the informativeness and accuracy of DNA based ancestry tests for Native Americans is highly dependent upon additional sampling of Native American individuals, which is contingent upon mutually beneficial relationships between private testing companies, universities, and Native American communities. Many Native American groups are understandably leery of the motives of private companies and government or university researchers. However a recent survey investigating the attitudes of Native American groups about genetic testing indicate that many Native American individuals do not oppose genetic research and believe they can benefit from it (Schroeder et al. 2004). To ensure that proper safeguards are in place to adequately protect Native American participants from the risks of genetic research, Native American communities would benefit from working with university researchers who are required to participate in human subjects protection protocols before proceeding with a project. Fortunately, the horizon looks bright for collaboration between Native American communities and university researchers on genetic research. Funding to initiate such collaborations is available through the National Human Genome Research Institute (NHGRI) and articles addressing issues of the best ways to proceed with such collaborations are becoming more frequent in the academic literature. Certain Native American communities are also taking a pro-active role in these collaborations and the direction and goals of research projects are being determined by Native American communities as well as researchers. Finally, it is up to the private DNA testing company to ensure that they are presenting the information about these diagnostic tests as accurately as possible. Due to the rapidly changing landscape of DNA based ancestry tests, private companies that are closely allied with university and academic research will likely be the companies with the best interpretation of the results from DNA based ancestry tests for Native Americans.
I see from one of the posts on RB that the following address is given for the Swiss company providing the latest funding:
http://ragingbull.lycos.com/mboard/boards.cgi?board=GMED&read=12336
Pierpoint Investissements SA
Trident Chambers
P.O. Box 146
Tortola
British Virgin Islands
A lot of companies use tax shelters and other offshore vehicles based in jurisdictions like the BVI. You would expect to find a lot of companies registered at this particular address, as indeed you can. Usually though different companies do not use the same P.O. Box number.
http://www.medico.de/kampagne/fatal/atpm.doc
Henry Guderley is also the company secretary of the London-based Essante Ltd, which is located at 40 Queen Anne Street, London W1. Sonia Falcone, of Paradise Valley, Arizona, is listed as the sole director of the company. The shareholding is more surprising: Sonia Falcone is listed as holder of one ordinary share, the other being held by Brenco Trading Limited, of Trident Chambers, PO Box 146, Road Town, Tortola, British Virgin Islands;69 an address shared by Copper Financial Inc, the listed owner of CADA Ltd (part of the Brenco network in Angola), of which Guderley is also the Company Secretary.52
According to a Swiss-based web site on money laundering issues, Geneva’s Chief Prosecutor, Bernard Bertossa, began investigations in January 2001 to determine whether Swiss banking facilities were held by individuals and companies whose names featured on a list for whom information was being sought.
I am sure this is just a coincidence though, here is another company using the same P.O. Box number:
Trident Trust Company (BVI) Ltd
Trident Chambers
P O Box 146
Road Town
Tortola
http://www.tridenttrust.com/
Personally though I would like to see a little bit more information about the mysterious Swiss financers...
OT bag8ger, tsk tsk! Have you no faith in market makers? God forbid that these bastions of the equity markets, these pillars of economic efficiency, these paragons of virtue and fair play, would stoop to such nefarious practices.
The range for the day was clearly 0.21 - 0.28. I do not know what that dip was but you can see it there on the chart I agree. It might have been a trade put through at a wrong price which was reversed but still shows on the chart. It doesn't appear on this Yahoo chart though:
http://finance.yahoo.com/q/bc?s=GMED.PK&t=1d
Another Shriver paper
Admixture in the Hispanics of the San Luis Valley, Colorado, and its implications for complex trait gene mapping. Bonilla C.; Parra E.J.; Pfaff C.L.; Dios S.; Marshall J.A.; Hamman R.F.; Ferrell R.E.; Hoggart C.L.; McKeigue P.M.; Shriver M.D. Annals of Human Genetics, March 2004, vol. 68, no. 2, pp. 139-153(15)
Bonilla C.; Parra E.J.[1]; Pfaff C.L.[2]; Dios S.[3]; Marshall J.A.[4]; Hamman R.F.[4]; Ferrell R.E.[5]; Hoggart C.L.[6]; McKeigue P.M.[6]; Shriver M.D.[3]
[1] Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada [2] Human Genetics Department, The University of Michigan, Ann Arbor, MI 48109-0618, USA [3] Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA [4] Department of Preventive Medicine and Biometrics, University of Colorado School of Medicine, Denver, CO 80262, USA [5] Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA [6] Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London WC1E7HT, UK
Abstract:
Summary
Hispanic populations are a valuable resource that can and should facilitate the identification of complex trait genes by means of admixture mapping (AM). In this paper we focus on a particular Hispanic population living in the San Luis Valley (SLV) in Southern Colorado.We used a set of 22 Ancestry Informative Markers (AIMs) to describe the admixture process and dynamics in this population. AIMs are defined as genetic markers that exhibit allele frequency differences between parental populations 30%, and are more informative for studying admixed populations than random markers. The ancestral proportions of the SLV Hispanic population are estimated as 62.7 ± 2.1% European, 34.1 ± 1.9% Native American and 3.2 ± 1.5% West African. We also estimated the ancestral proportions of individuals using these AIMs. Population structure was demonstrated by the excess association of unlinked markers, the correlation between estimates of admixture based on unlinked marker sets, and by a highly significant correlation between individual Native American ancestry and skin pigmentation (R2= 0.082, p < 0.001). We discuss the implications of these findings in disease gene mapping efforts.
There are two "new" names on this paper, Richard Hamman:
http://www.uchsc.edu/pmb/epi/rfh.htm
and Julie Marshall:
http://www.uchsc.edu/pmb/epi/jam.htm
Theo, all we know is that Arena (and Mirhashemi) were previously listed on the Scientific Advisors page and now they are not.
St Louis Business Journal article
This one doesn't add anything to what was in the press release. I note that Dr Moskowitz said this will allow the company to "move forward with its scientific program and its marketing strategy to physicians and patients nationwide." There is no reference to the Malaysian partnership here.
http://stlouis.bizjournals.com/stlouis/stories/2004/03/01/daily41.html?jst=b_ln_hl
GenoMed gets long-term financing commitment
Pierpoint Investissements SA, a Swiss-based venture capital group, has agreed to provide long-term finding to St. Louis-based GenoMed Inc., the company said Wednesday.
Pierpoint will make a minimum annual investment of $500,000 up to a maximum of $2 million a year for each of the next 10 years in exchange for 12-month restricted shares at a discount to market price. Pierpoint will also hold active warrants for another 35 million shares, which can be converted only when GenoMed's stock price reaches at least $1, at a rate of 7 million warrants a year.
Dr. David Moskowitz, chief medical and chief executive of GenoMed, said the financing allows the company to move forward with its scientific program and its marketing strategy to physicians and patients nationwide.
St. Louis-based GenoMed Inc. (Pink Sheets: GMED) is a medical genomics company working to find genes that cause disease. The company's shares closed March 2 at 12.3 cents.
Frog, it does, but it is easier to see the point in context (even if you have to sift through some 120 pages to appreciate it lol).
Frog, you might want to read the whole thing i.e. in context and see what they are saying.
What about those claims Mike?
TonyTox might be interested in this one:
"However, as promising as that MALD approach appears, until the present disclosure, no systematic screen has been reported identifying SNP based versions of the AIMs required. McKeigue and others have identified panels of STR AIMs for use with this approach, but the use of STRs for this purpose is problematic because of the allelic complexity of STRs and the massive databases required in order to accurately estimate allele frequencies. Even small errors or faulty assumptions on the frequencies of unobserved alleles can amplify to cripple the statistical power of a study."
If it's good enough for Slopster...
Look again. I spent over 3 hours reading it this morning (and the rest of the day thinking about it).
Investigators generally have been concerned with identifying gene variants that cause a disease (the so called"phenotypically active"loci), rather than identifying gene variants that are simply correlated with disease.
"...compositions and methods are provided for inferring an individual's response to commonly used medications, which, remarkably, is a function of individual ancestry;"
This bit, although minor in comparison to others, has a certain Je ne c'est quoi:
"There is much that can be learned today through the use of genetic markers in numerous scientific fields. The use of genetic sequences has become routine for forensics and disease research, but the majority of the benefits from the recently completed human genome project still await discovery. Within the genome exist sequences and patterns of sequences that will prove useful for a variety of purposes including increasing crop yields, extending human life spans, minimizing the suffering caused by drugs and enhancing the quality of our lives through better, more effective and specific treatments."