23andMe: Forcing Old Docs to Learn New Tricks

by Krishan Kania

23andMe, a California based startup co-founded by Anne Wojcicki, offers a direct-to-consumer Saliva Collection Kit and Personal Genome Service (PGS), which since its launch in 2007 has genotyped approximately 500,000 individuals.  To be clear, 23andMe does not sequence complete genomes, but rather, offers a SNP (single-nucleotide polymorphism) DNA test that instead records what are arguably the most important 1 million “snips.”  And while amounting to less than a thousandth of a percent of the total genome, these snips have been proven to be very informative in describing one’s unique risk of genetic disease, drug response, personal traits, and ancestral information.  Such insights are supported by a strong body of scientific literature, which the scientists and physician-scientists at 23andMe use to interpret raw data (all those SNP’s) into clean, protected, and user-friendly reports on health and ancestry. 

However, in November of 2013 the Food and Drug Administration (FDA) warned 23andMe to stop offering its primary service of providing users with a health report on 254 genetically related diseases and conditions.  Following the argument that PGS is a “medical device” without government approval, the FDA goes on to describe “the potential health consequences that could result from false positive or false negative assessments for high-risk indications.”  For example, if a woman sees that she is at risk for breast cancer based on an unfavorable mutation in her BRCA gene (a gene associated with breast cancer) detected by the 23andMe assay she may be inclined to undergo prophylactic surgery, chemoprevention, or intensive screening.  With that said, according to the FDA, it is possible that this woman does not actually have nor will develop breast cancer— a false positive.  Fearing that customers could make rash decisions based on their 23andMe health report and thus pursue such expensive and potentially dangerous treatments, the FDA decided to ban 23andMe’s flagship service.  And so as of February 2014, 23andMe is able to offer ancestry-related reports and raw genetic data, but unable to offer a health report.

Personally, I think there are reasonable causes for public examination and regulation of 23andMe, as there should be with any company diving into an unfamiliar and uncharted market, however promising or exciting as their service may be.  At the same time, I believe that the FDA is unfairly treating PGS as a medical device and unwisely pursuing a legal ban.

To expound on the first point, 23andMe is an information driven company collecting particularly sensitive and complex information.  And like Google, it is likely that the value of this company is not based upon the service it offers to any particular end user, but rather the information it is able to gather in aggregate.  So while collecting DNA from all over the United States could bring us new insights fueling our efforts to advance science research (population genetics, drug discovery) the sale of such information could be equally dangerous. 

Furthermore, such a service presents an important ethical question: are we entitled to the information encoded in our DNA?  Technically, DNA is what we have inherited from our parents and it is something we share to a varying degree with our siblings, cousins, and relatives.  As noted by Charles Seife in an article published by Scientific American, using 23andMe may feel like a personal decision, but in a sense, it also grants investigators the implicit consent of family members of generations past, present, and future.

Still, it is not necessary that in regulating these issues (among others), that the FDA has to ban this service.  First and foremost, treating PGS as an untested medical device is unfair and implies very little respect for the American public and practicing physicians.  Returning to the hypothetical false-positive, it is worth distinguishing between phenotype and genotype.  On the genetic level, it is highly unlikely that 23andMe calls a false-positive in the sense that the sequencing assay falsely calls the wrong mutation at the particular SNP for the BRCA gene.  Such sequencing technologies are designed with accuracy as the chief concern, and thus built with in an error rate of around 1 in 7,000— this would easily make PGS to be the most accurate “medical technology.”  So perhaps, the FDA was referring to a false-positive in the sense that the genotype is right but the phenotype is wrong.  Well, 23andMe is by no means claiming that a user has breast cancer, but instead, just noting a level of risk.  It is highly unlikely that a doctor in the United States would perform any serious surgery or complicated screening on the basis of 23andMe alone. 

Last, by banning the service, the FDA has inadvertently created a void that will be filled by uncontrollable, smaller parties.  At the moment, users of 23andMe can access their raw data, but the experts at 23andMe cannot interpret this data into a comprehensive health report.  Consequently, users may be tempted to interpret their data for themselves based upon scientific literature published online.  Perhaps there will even be a demand for third-party businesses to form, specifically designed to interpret raw data reports from 23andMe.  As more of these situations arise, the FDA will have increasingly less control in matters of regulation. 

As mentioned earlier, there are compelling issues yet to be addressed regarding the potential misuse of genetic data, but my hope is that sooner, rather than later, the FDA revokes its ban.  Given a more friendly relationship between both parties, I am optimistic that they can work together to set a historical precedent, marking the early beginning of consumer genetic testing.

A Child’s Right to Die

by Samantha Cody

A recently proposed addendum to a 2002 Belgian euthanasia bill extending euthanasia rights to children has – not surprisingly – been causing a lot of turmoil this winter. The tenets of the bill strive to broaden the array of options available to children in dire straits by allowing them the same right to die currently held by adults. The amendment to the law allows any child enduring “constant and unbearable physical suffering” and with “capacity for discernment” to make the decision, with parental consent, to end his life.  

            The basic principles of the general controversy over euthanasia rest on considerations of the rights of the two people involved: the patient, and the physician. Proponents of euthanasia back the concept on the grounds that a terminally ill patient or one enduring an inordinate amount of suffering should have the right to end their suffering in a humane, dignified manner. Opponents of the idea emphasize the role of the physician, particularly given a physician’s duty to extend the patient’s life for as long as possible, and express concern over the potential for abuse of hypothetical legislation.

            Belgium is a pioneer in euthanasia legislation amidst a host of substantially warier neighbors. The debate over the most recent amendment has sparked the attention and fervor of physicians, legislators, and religious leaders alike. Opposition to the amendment is primarily structured around concern over a child’s ability to make the decision to end his/her life. Attention has repeatedly been called to the lack of consistency in allowing children to make the decision in question while continuing to consider them legally incapable of making decisions in other areas of criminal and civil law, such as marriage. Many are also leery of how nebulously defined “capacity for discernment” is, particularly in considering whether or not a child fully understands the implications of choosing to end his/her life. A number of legislators and religious leaders believe that children will inherently be vulnerable to pressure and as such, cannot be trusted to have full autonomy of choice. Those who back the bill have been very responsive to the opposition. Many argue that given that adults are granted the right to die, it is unjust to thereby deprive another percentage of the population that right. Most supporters of the bill see it as a way of giving children compassionate options in desperate circumstances rather than forcing them into painful or unbearable circumstances, such as enduring a great amount of ineradicable suffering for lack of other options. Physicians, rather than evading the claims of the opposition that “capacity to decide” is simply too ambiguously ascertained, acknowledge the difficulty in such judgment, but claim that experience has shown that in the face of death, children can often be seen to develop an abnormal maturity and ability to reflect.

Thus far in the senate, there is an overwhelming large amount of support for the bill, with only 17 of the 71 members voting against the measure.

From Acid to Embryos

by Jennifer Au

Stem cell research has taken a huge leap. Haruko Obokata, a researcher at the Riken Center for Developmental Biology in Kobe, Japan, astounded the scientific world when she published an article explaining her work on creating stem cells from white blood cells from mice, using a little bit of acid. Obokata tested a variety of different stresses on the blood cells, in hopes that one of these stresses would induce totipotency. She found that when the cells were placed in citric acid of pH 5.7 for 30 minutes, the cells started behaving like stem cells after a couple days. To prove these were in fact stem cells, Obokata grew entire mouse embryos from these cells, effectively putting to rest any doubts in her discovery. This finding is followed by another from a Japanese and American team, which used the same technique, but this time utilized human skin cells to produce stem cells that have the potential to develop into human embryos.

The simplicity and elegance of this technique does not come without controversy. With this is the fear of cloning. This procedure effectively allows for an exact copy of a person to be grown from a couple of cells. While scientists do not plan to head in that direction, and would surely face overwhelming opposition if so, just the prospect of copying and producing an exact replica of a person from something as simple as a skin cell has stimulated debate. It begets the question: how far is too far? Humans have a long history in altering and disturbing nature, but the possibility of creating another person artificially is where many draw the line.

However, this does not mean this technique should be tucked away and locked in a vault, never to be utilized by man. The implications of this are far and wide and could begin a new era of medical treatment. The ability to create stem cells from a fully differentiated cell means any type of cell, whether it be heart, liver, or any of the body, can eventually be produced. This could effectively eliminate the issue of tissue rejection, as cells can be taken from the patient and grown into a new organ with the patient’s own DNA and markers. The simplicity of the technique leaves the scientific world hopeful, and could solve the central controversy of embryo use in stem cell research, which could lead to freer research and greater changes in medicine.

Sources:

http://www.npr.org/blogs/health/2014/01/29/268171016/a-little-acid-turns-mouse-blood-into-brain-heart-and-stem-cells

http://www.independent.co.uk/news/science/exclusive-the-miracle-cure--scientists-turn-human-skin-into-stem-cells-9117102.html

Fair or Foul: Legalizing PEDs in Sports

by Ian Kinn

As it pertains to sports, a performance-enhancing drug is any substance which is used to augment the athletic ability of an individual.  Often referred to simply as PEDs, these drugs have long been utilized in athletics, from high school to a professional level.  Common examples include anabolic steroids, human growth hormone (HGH), amphetamine, and many other substances which have been banned in most professional and amateur sports.  Although they have been proven to enhance the athletic ability of individuals, PEDs come with a plethora of negative side effects, ranging from deepening of the voice to liver damage.

The primary criticism of PEDs is the unfair advantage they provide to individual athletes with respect to their “unenhanced” competitors.  However, if PEDs were legalized in sports, it would eliminate the advantage that any player could obtain over another, as everyone would have equal access to the substances.  Sports, especially professional ones, are by nature extremely competitive.  Enhancements are made in many ways, which are far from limited to just drugs.  Who is to say getting a leg up on an opponent through a PED is any different than having the advantage of better facilities and trainers than other athletes?  There are many different ways in which athletes gain an edge on the competition which could also be considered unfair.

Certain PEDs can undoubtedly have a negative impact on a person’s health.  However, it is each person’s right to determine the risks that they are willing and able to take in all other aspects of life, so it should be no different when it comes to increasing their performance on the field or the court.  If someone deems the potential rewards of taking PEDs greater than the risks, it is their right to do what they want with their body.  There is no potential of harming anyone but themselves.  Also, the sports industry is a business by nature, and PEDs have the potential to increase the entertainment value of every sport.  Viewers would be fascinated by longer home runs, high-flying dunks, and faster athletes.  Some of the most captivating sports stories have been brought about by the use of PEDs.  The race between Mark McGwire and Sammy Sosa in 1998 and Barry Bonds’ home run spree a few years later remain as two of the most popular moments in baseball history, both of which were catalyzed by the implementation of PEDs.  By doing things which were previously unimaginable, they fascinated fans across the world and brought baseball’s popularity to a whole new level.

The line between legal and illegal substances in professional sports is already very gray and impossible to explicitly define.  An athlete such as Dwyane Wade can receive a Cortisol shot in his knee to help him play through the pain in the NBA playoffs, yet it is illegal to take certain drugs (such as HGH) which would help him to actually heal faster.  Legalizing PEDs would allow athletes to play and feel their best while entertaining the fans to the best of their abilities.  It would also save time and money, as the investigative committees would no longer be necessary.  Many people believe PEDs to be immoral and unsportsmanlike without basis.  Professional sports are all about doing whatever it takes to gain an advantage over your opponent.  Performance-enhancing drugs should be legalized in all professional sports, as they would increase the quality of sports and remove all suspicions of “unfair” play.

Sources:

http://www.usada.org/effects-peds/

http://sportsanddrugs.procon.org/view.resource.php?resourceID=002352

Organs on a Chip: The Future of Clinical Trials

by Adam Bowman

Pharmaceutical companies face dense regulatory bureaucracy and dozens of competitors seeking to fast-track their drugs to the market. Such competition and red tape leaves little room for new methods and necessarily slows the pace of drug development. Researchers have proposed a new device which they hope will replace animal testing and reduce risks in phase I clinical trials. This device is a 1/1000 scale human – small enough to fit on a desk. It will have a beating layer of heart cells, breathing lung cells, and a blood-brain barrier interconnected with other organs just as if they were in vivo – including the spleen, pancreas, and gut to name a few . This microfluidic human would be a fully automated drug discovery platform – streamlining the drug testing process, reducing risks in clinical trials, and cutting costs for pharmaceutical research.

What we do now:

Drugs undergo extensive animal testing in the laboratory before approval for human trials at sub-clinical doses. The details of stage I human trials are heavily debated in bioethics, and animal testing is equally controversial. This guess-and-check method of drug development has been the model for decades, but presents dangerous problems while clogging the pipeline for promising drug developments. Researchers like Don Ingber and John Wikswo argue it is time for a change.

Why it fails:

Animal and human organ systems are simple not equivalent. Predicting how organs in a human will interact and communicate based on a mouse model leaves dangerous assumptions when entering phase I trials.  In some cases, the health of the trial subjects can be seriously endangered. In 2006, the trial antibody TGN1412 for the treatment of autoimmune disorders went from animal testing to phase I clinical trials on six volunteers in sub-clinical doses. Despite doses 500 times smaller than those found safe in animal trials, all volunteers faced life-threatening conditions due to systemic organ failures. Failed trials like these increase the regulations, time, and costs involved in approving drugs, inhibiting promising developments.

Why the micro-human?

Ingber, Wikswo, and others are involved in an effort to build a micro-human composed of multiple organs-on-a-chip to reduce costs and risks in drug trials. The micro-human is platform of interconnected microfluidic chips, pumps, valves, and sensors which mimics the essential functions of the body’s organ systems. From a beating layer of heart cells to active diffusion across a simulated blood-brain barrier, the micro-human or homunculus is the state of the art in biomedical engineering. Ingber began the work by building an artificial lung-on-a chip at Harvard. Using vacuum and fluid channels and a thin membrane of lung cells within a flexible polymer mold, Ingber’s chip replicates the human lung alveolus, including blood flow and rhythmic pumping. An entire human organ system can fit on a desk and contains all the inter-organ links needed for a simple human analog. The active biological mass of the system is only 70mg, one millionth the mass of a human. Drugs tested on such a platform could be carefully assessed on human cells without the ethical complications of phase 1 trials. For example, side effects of a heart treatment on the blood-brain barrier could be noted, or dangerous chemical combinations identified. The National Institutes of Health (NIH) and Defense Advanced Research Projects Agency (DARPA) have issued over $137 million dollars to fund organ-on-a–chip research since 2012. The micro-human may soon have macroscopic consequences at your local Walgreens.

Sources:

http://www.npr.org/2012/07/27/157489675/building-organs-on-one-microchip-at-a-time

http://news.vanderbilt.edu/2012/07/microbrain/

http://cosmiclog.nbcnews.com/_news/2012/07/24/12930646-federal-agencies-kick-off-132-million-effort-to-create-human-on-a-chip

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964774/

http://blogs.rsc.org/lc/2013/08/01/engineering-the-%E2%80%98microhuman%E2%80%99/

Title?

by Kathy Chow

Before any drug reaches the sales counter, the Federal Drug Administration (FDA) must approve it via a three-phase process to ensure that it is safe for consumers. This is a long and arduous process that usually takes several years.

The question of whether we should allow terminally ill patients to gain access to non-FDA-approved drugs is one that has surfaced repeatedly in recent years. In 2008, the Supreme Court justices dismissed Abigail Alliance v. von Eschenbach. As a result, a divided federal appeals court made the decision instead, ruling that terminally ill patients do not have the right to use experimental medications. More recently, during the 112^th Congress (2011-2013), Senator Ron Paul attempted to introduce the Compassionate Freedom of Choice Act, which would prevent the FDA from restricting access to experimental medication for terminally ill patients. However, the bill died in committee.

Despite the continuous rejection from various branches of the United States government of this policy, several compelling arguments may be made in its favor.

First, there is the issue of bodily autonomy. The ability to make independent choices gives human life meaning. If you woke up one day and somehow realized that your brain is hooked up to a machine that generates your perceived “reality”, your life would have a lot less meaning. Why? Because the decisions that you think you made were not actually made by you, but were instead predetermined by the machine. Therefore, you will realize that what you once perceived as a journey involving choices at several intersections that lead you to a destination you choose for yourself is in fact a single road the destination of which has already been determined. In sum, the more choices you have, the more meaning you have in your life. Consequently, what we see with this proposal is an increase in the quality of life in general for terminally ill patients because it allows them to exercise the right of bodily autonomy.

Furthermore, the terminally ill deserve respect and trust, which are closely correlated with how much autonomy we give people. For example, the government incarcerates criminals because we cannot trust these people with their autonomy and their ability to make choices that don’t negatively impact society. However, in the situation of the terminally ill who are innocent and have not shown any tendencies to make poor choices that cause harm to others, the government removal of such an important and potentially life-saving choice from their lives essentially tells them that we do not trust or respect their abilities to make their own life decisions. Consequently, the government would be grossly overstepping its role.

In addition to the moral arguments, a persuasive case can be made from a pragmatic perspective as well. To begin, the FDA takes an extremely long time to approve a drug. This occurs because there is strong incentive for them to be as thorough as possible: to minimize the risk of wrongfully approving a drug that is in fact more harmful than helpful and inspiring mass criticism from the public. At first glance, the meticulousness of the FDA may appear beneficial for society because it ensures that only the drugs with proven benefits that far outweigh any possible negative side effects will enter the market. However, one must realize that in the case of terminally ill patients who essentially have no other choice, the extreme length of time taken by the FDA to approve a drug is essentially a death sentence for them. Thus, by giving terminally ill patients access to non-approved drugs, the government at least gives these people a chance to live.

http://www.nytimes.com/2008/01/15/washington/15appeal.html?_r=0

https://www.govtrack.us/congress/bills/112/hr6342#overview

Should Plan B be available over the counter?

Plan B, also known as the “morning after pill”, is currently available over the counter in the U.S. to anyone over the age of 17. The Food and Drug Administration (FDA) gave their public support to the Center for Reproductive Rights’ motion to make the drug available to all women without a prescription, arguing that it does not terminate pregnancy the way other pills such as RU-486 (“the abortion pill” that can be taken up 9 weeks after conception) but merely provides a higher dosage of birth control hormones to prevent pregnancy within 72 hours of unprotected sex. It is considered safer than Advil. Two weeks ago, the motion to eliminate the age restriction on the morning after pill was contested by the secretary of Health and Human Services Kathleen Sebelius, who spoke up against it stating that young girls would not be capable of understanding how to use it correctly and should not have access to it without a physician’s consent.

President Obama had lowered the age of accessibility to Plan B without a prescription to 17 shortly after he took office but this time around sided against the FDA, agreeing with Sebelius that the age restriction is fundamental.

Judge Edward Korman of the Federal District Court ruled against Sebelius, and ordered that the drug be available to all Americans within the next month.

The question of accessibility to birth control has always been controversial, and this time around is no different. The risk associated with eliminating the need for a prescription is that extremely young girls (as young as 11) can purchase the pill without anyone knowing or explaining to them what exactly they are taking and how it works. Like all other drugs, although it is considered very safe by the FDA, Plan B can have negative side-effects if not used correctly - altering the hormone dosage of a child’s body is not a light decision to make. On the other hand, making every girl under the age of 17 have to acquire a prescription from a physician before taking the drug can lead to much worse scenarios: girls who are in a situation in which they might need Plan B are most of the time embarrassed and afraid. Being too scared to tell their parents or any other adult including a doctor could lead to waiting too long and having to get an abortion later on if that is the case. The issue about the morning after pill is precisely what its name entails: time is the key factor. Waiting more than 72 hours can lead to inefficiency and more invasive procedures at a later stage of the pregnancy.

Although the thought of young girls buying Plan B without fully understanding its use is heartbreaking, what should be addressed is the root of the problem. By educating women, we can empower them and help them make decisions that are safe and healthy. But as long as young girls are having unprotected sex, taking the morning after pill is still the safest and most reliable option, and should therefore be available to all.

Sources:

http://www.chicagotribune.com/videogallery/75333635/Plan-B-controversy-reignites-science-debate-in-Congress

http://www.cbs12.com/news/top-stories/stories/vid_6436.shtml