- self-renewal

- undifferentiated status -- ability to differentiate

- pluripotency: having more than one potential outcome

- can replicate themselves over and over for a very long time

- understanding how stem cells develop into healthy and diseased cells will assist in the search for cures

- have the potential to replace cell tissue that has been damaged or destroyed by sever illness ("regenerative medicine")

- "excess" fertilized eggs created in the process of IVF practice, ie eggs donated, frozen eggs in IVF clinic

- fertilized eggs or human cloned embryos created for research purposed only

- regenerative medicine could be breakthrough in future medicine

- hESC research usually destorys human embryo

- requires egg donation

- brings about excessive hopes and hypes

SCNT

Somatic Cell Nuclear Transfer

current federal policy on hESC research

- not illegal at the federal level but funding is only approved for stem cell lines derived prior to Aug 9, 2001

- in order to obtain federal funding: stem cells must have been created for reproductice purposes and was no longer needed and informed consent must have been obtained for the donation and must not have involved financial inducements

- prohibits funding for :

1. creation of human embryos for research purposes

2. research in which embryos are knowingly destroyed or put at risk of being discarded

3. This includes an embryo derived from fertilization, parthenogenesis, cloning, or any other means from one or more human gametes or diploid cells

iPS cells

Induced Pluripotent Stem Cells

- iPS cells could generate patient specific cells for research/clinical purposes w/out destroying human embryos

- regenerative medicine using iPS could replace that of SCNT in the future

- iPS has problems and while these remain unsolved hES cells should be used for  translational research

- hES cells can be used as controls to examine safety and abilities of human iPS cells

- some important areas of research that can't be accomplished by iPS but can be hES cells

- monitoring the brain: neuroimaging

- advanced brain therapy: cell therapy, DBS and psychopharmacology

- Manipulating the brain: brain-computer interface, neurochip,

BCI - Brain Computer Interphase and Neurochip

- both used to augment human potential; for clinical purposes or for educational, commercial, military, and other (brainwashing) purposes

-Neurochip: Controls human behaviors and performances; implanted chip to record activity in a person's brain

- Clinical: diagnosing brain cancer/other neurological dieases

- Research: educational tracki/]ng of school children, investigate relation between brain activity and a person's character traits/ behavior tendencies

-Commercial/Other: detecting hyperactivity/learnding disorders, lie detection

- Incidental Findings

- Stigmitizing: insurance companies/ finding uber talented kids

- Privacy: data on one's brain considered ultimate private info? 

- stem cell transplants could be used to treat patients with degenerative neurological diseases such as Parkinson's and Alzheimer's

- could be used to "cure" brain-damaged persons or infants

- a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain

- being used for Parkinson's, Dystonia, OCD, Depression, Tourette's

- side effects: physical changes, cognition changes, mood/behavioral changes

Lewis DO et.al. Am J Psychiatry 1985. What they investigated and what they proposed/justified

- studied the biopsychosocial characteristics of children who later murder

- proposed: when the constellation of psychotic symptoms, severe neuropathology, and the existence of psychotic, abusive family members is identified in an already violent youngster responsible intervention is justified

- became popular in the 19th century

- the shape of the brain determines the brain's functions

- Franz Joseph Gall and Johann Gasper Spurzheim

- brain-dissecting method

- a "fad"

- DBS and psychosurgery are different: DBS does not involve irreversible lesions

- It all comes down to risk-benefit analysis

- while at an investigational stage, physician-scientists should carefully evaluate the effects of DBS on a patient's mood, cognition, and behavior

- "[although] present procedures are so far from what we wish is no reason to give up hope of their improvement."

- leucotomized patients are often compared to a vegetable becoming more egoistic, tactless, dull, and lazy

- in the case of chronic psychotic patient common humanity would justify an extreme measure if it offers hope

- function of surgeon: hazards of leucotomy, social and physical complications reduced to a min

- function of psychiatrist: select patients who will benefit most from operation before deteriorating and desocializing have ruined life

- function of physician: find new/better methods of treating patients who occupy more than 1/2 hospital beds

- 1936 est. lobotomy/leukotomy 

- pioneer of cerebral angiography, now the gold standard for detecting vascular abnormalities in the brain

- developed angiography and killed patient then succeeded in 1972

- DBS: rarely causes irreversible lesions/but electrodes may be displaced, can cause person changes but extent unknown

- lob: involved irreversibly lesions, cause mid/severe person changes explained as inevitable

- Similarities: could bring more benefits than risks, only treatment-resistant patients, last resort

- surgery to damage a certain part of the limbic system that contains structurally normal brain tissues, with the intention to suppress abnormal feelings or behavior caused by psychiatric disorders

- lobotomy est. by Dr. Egaz Moniz in 1936 and refined by British psychiatrists and by Freemand and Watts in the US

- aka embryo screening

- procedures done on embryos to avoid selective pregnancy termination

- a method to make the baby free of disease

- requires IVF in order to evaluate embryos

- sex ID to avoid transfer of X-linked genetic diseases

- detect aneuploidies (abnormal # chromosomes), monogenic diseases CF/ Tay-Saches

- select embryos that would be compatible tissue donors for older siblings in need of transplants

- elective sex selection

- should not be treated as experimental but clinical and therefore may be practiced w/out IRB

- regards sex selection as ethically acceptable for medical indications but not elective purposes

- one paper said ok for elective sex selection if the reason is to add variety to family

- sex selection okay to avoid sex-linked disease but not gender preference

- ok to inseminate for single women or homos

- ok to participate in genetic selection to prevent, cure, or treat genetic diseases; however selection to prevent genetic disease may not be ok depending on severity, age of onset, probability, tine of gestation/ never ok if not disease related

- allows use of PGD for detecting genetic diseases

- not to make savior baby when parents are not carriers of disease or purely gender selection

How PGD dealt with in France

- no gender selection

- gender selection ok to prevent gender related diseases

- PGD permissable only for medical purposes

- highly governed/scrutinized

- polar body diagnosis welcome

- allowing sex selection will open the door for trait selection

- children will become commodities paying a commercial industry for a service dehumanizes people

1.Reduction - in the # of animals

2. Refinement - of techniques that cause suffering or stress

3. Replacement - of living animals by simulation, cell culture or other non-animal models

-  the procedure applies a test substance to an animal's eye or skin for four hours, animals observed for signs of erythema and edema in the skin test, and redness, swelling, discharge, ulceration, hemorrhaging, cloudiness, or blindness in the tested eye

- LD50: how much of a substance causes death

- arguments questioning necessity of animal experiments: results are often inapplicable to humans, infrastructures are more important that medical research, look at reality of animal experiments

- efficacy argument: best results/best kept animals

-"the relationship of mutual trust" between humans and animals

- arguments to sympathize or empathize w/ the feelings of animals

- Animal Rights: humans/non-humans should be treated as equally qualified for moral consideration

- Equal Consideration: it is cruel to make animals suffer just as it is cruel to make humans suffer; considers SUFFERING over equality

- human care/treatment provided for dogs cats nonhuman primates guinea pigs hamsters rabbits and other warm-blooded animals; birds rats mice bred for research not considered animals

-

Animal Welfare Act - standards for humane handling, care, treatment, and transportation of animals

1) physical environment to promote psychological well-being

2) min. of animal pain/distress

3) in pain-causing research consult veterinary

4) animal cannot be used in more than 1 experiment w/out time to recover

5) no exceptions unless specified by research protocol and approved by Institutional Animal Committee

PHS Policy on Humane Care and Use of Laboratory Animals

- to what kinds of animals this policy applies

- How often IACUC is supposed to review programs

- animal denotes any live vertebrate animal used or intended for use in

- Institutional Animal Care and Use Committees to review at least once every six months

"The Guide"

- what kinds of animals this applies

- what kinds of topics should be considered in preparing and reviewing proposals for animal care and use

- any lab vertebrate animal used in research

- rationale/purpose of proposed use of animal, justification, availability of alternatives, adequacy of training/experience of individuals, unusual housing/husbandry requs, approp sedation, unecessary duplication of experiments, conduct of multiple major operative processes, process for timely intervention, post-procedure care, method of ethanasia, safety of environment/personnel

- a fed contractor can take ownership of the property rights for the inventions created in the pursuit of a grant/contract

- the income from the use of intellectual properties must be shared w/ inventor and the remainder must be used for research or educational purposes

Different kinds of Conflicts of Interests

- a researcher's (or relatives) personal/financial interest by exploiting his position vs. public well-being

- an institution's financial interest vs. interest of others

- creating an appearance of a conflict of appearance

Patent System

What it gives a patentee in exchange for what

- gives a patentee a legal right to exclude others from making/using/selling invention IN EXCHANGE for the patentee's full disclosure of the reproducing method, the function, and use

- inventor's right to benefit from invention

- others can utilize their findings/ researcher's compete to attain new findings

1) Useful

2) Novel

3) Non-Obvious

4) Described in sufficient detail to enable other skilled persons in the field to use it for stated purpose

- Chakrabarty created a bioengineered microbe that can dissolve crude oil, useful to treat oil spills

- patent denied

- court ruled that a live, human-made, micro-organism is patentable because they do not occur naturally in nature

HIV/AIDS stands for

what cells HIV targets ?

- human immunodeficiency virus: mainly targets T lymphocytes (T-Cells); mature in the thymus

- Acquired immunodeficiency  Syndrome

- Swaziland: 33.4 %

- Botswana: 24.1%

-Lesotho: 23.2%

Sub-Saharan African Countries

Ethical Issues in HIV/AIDS in General

- Deliberate Infection of Others

- Discrimination against HIV-positive individuals

- fear of medical professionals to treat HIV/AIDS patients at risk of infecting themselves

- Obligation of medical/healthcare professionals to prevent worldwide spread of HIV through education and research etc.

CIOMS International Ethical Guidelines

(there's eleven)

1. ethical justification/scientific validity of biomedical research involving human beings

2. Ethical review committees

3. ethical review of externally sponsored research

4. Individual informed consent

5.essential info when obtaining IC

6.obligations of sponsors/investigators when obtaining IC

7. Inducement to Participate

8. Benefits/risks of study participation

10. Research in populations and communities with limited resources

11. Choice of control in clinical trials

21. Ethical obligation of external sponsors to provide health-care services

- Fabrication: making up data/results

- Falsification: manipulating research

- Plagiarism: taking another's ideas

*research misconduct does not include honest errors or differences of opinion

Regulation 42 CFR Parts 50 and 93

"Public Health Service Policies on Research Misconduct: Final Rule"

- adopts the same federal definition of research misconduct

- applies to biomedical or behavioral research/training or activities related to that research or research training that are supported by PHS or that are under consideration for PHS support

- to develop policies to detect research misconduct

- to review research misconduct investigations

- to provide technical assistance to institutions that respond to allegations of misconduct

- to offer education to promote integrity

Step 1. Peer Review process in grant application

Step 2. Referee examination and an editor's judgement for papers submitted to a scientific journal

Step 3. Test of replication

Ethical Issues of HIV/AIDS Research in Developing Countries

(there's seven)

1. Obtaining IC when participants are illiterate or have different opinions/ideas of autonomy

2. Following ethical guidelines of developed world or developing world

3. Researcher's pursuit of more effective but more expensive therapy or less effective but more affordable

4. When research is conducted in developing countries, how much should be patients be compensated for adverse effects?

5. Particpants recieving therapy post research

6. Researchers disclosing findings to host country

7. Should researcher's study strains of HIV not prevalent in the US?