Sweet, Soft Matter: Candy Cotton for the Regeneration of Blood Vessels

I love interdisciplinary journals, but I had not stumbled across Soft Matter, where physics meets chemistry meets biology for fundamental soft matter research, until today when the following story caught my eye:

(Via Red Orbit)

"Scientists are turning to cotton candy as a novel tool to help grow replacement tissues for people. It seems the long-time favorite treat may provide an ideal way to generate a network of blood vessels within lab-grown skin, bone, muscle or fat for breast reconstruction, researchers say.

Dr. Jason Spector of New York-Presbyterian Hospital/Weill Cornell Medical Center in New York and Leon Bellan of Cornell University conducted the research on the new technique.

It works by first pouring a thick liquid chemical over the cotton candy, and waiting for the liquid to solidify into a chunk. The chunk is then put in to warm water to dissolve the cotton candy, leaving small channels where the strands of cotton candy used to be. Eventually, what is left is a piece of material containing a network of fine channels.

These channels are then lined with cells to create artificial blood vessels. The solid chunk can be seeded with immature cells of the type of tissue scientists wish to make.

Since the block is biodegradable, as it disappears it is slowly replaced by growing tissue. Ultimately what remains is a piece of tissue permeated with tiny blood vessels."

Assuming this technique will be refined, it would have incredible implications for organ transplantation, regenerative medicine, artificial wombs, as well as other medical uses.

What can I can say but "Sweet!"?

U.S. Court of Claims Denies Claim of Vaccine/Autism Link

A specially convened vaccine court, part of the process required to seek compensation under the Vaccine Injury Compensation Program, has ruled against parents saying that the MMR vaccine caused autism in their children. The court specifically said that there was absolutely no compelling scientific proof of the claim, and that the "petitioners' theories of causation were speculative and unpersuasive."

This was one of three test cases going before the court, and the court has yet to rule on the claim that thimerosal alone is the culprit. However, the language the court used in this case is very telling: "The petitioners have failed to demonstrate that thimerosal-containing vaccines can contribute to causing immune dysfunction."
-Kelly Hills

Why I Love Designer Babies

Perhaps I should say I love the topic of designer babies, which is why I was pleased to read Gautam Naik’s provocative article, “A Baby, Please. Blond, Freckles -- Hold the Colic” in the Wall Street Journal today. Naik points out that this technology is nearer than we think; he reports on a Los Angeles clinic which will soon help couples select both gender and physical traits in a baby when they undergo a form of fertility treatment. Researchers from Harvard to Stanford and around the world are working hard to make genetic modification a reality. Are we ready?

Genetic modification and selection raises a number of issues that we at the Women’s Bioethics Project believe should be at the forefront of any good bioethics discussion. Here’s why:

1) It’s a hive of ethical issues
Genetic modification and selection raises a whole slew of ethical issues: how we view our children; where we draw the line at enhancement v. therapeutic applications of the technology; the issues of safety, access, and social justice; and the potential eugenic applications, just to name a few.

2) The technology isn’t here yet
Because the technology isn’t available yet, there is still a chance to consider the implications before wide-spread use. A tremendous amount of scientific progress in the area of cloning has been made since the 1997 announcement that a sheep had been successfully cloned; cloned primates and pets and the creation of induced pluripotent stem cells and human-nonhuman chimeras are just a few of the scientific discoveries that get us closer every day to the prospect of a genetically modified child.

3) We all have a stake in the issue
The ability to radically alter human reproduction raises fundamental questions regarding the nature of our humanity and the character of our society. All of us, whether we choose the use the technology or not, have a stake in the genetic modification of children and we need to engage in conversation on these issues now.

4) Questions raised go beyond designer babies
I love the topic of designer babies because difficult questions need to be asked about all kinds of emerging technologies from nanotechnology to therapeutic and reproductive human cloning. It can be overwhelming, but the only thing we can count on is change–that the nature of the technology will evolve while the challenges remain.

Moving forward
As we discuss genetic modification, we must remember that this not just an interesting a moral philosophical exercise—our elected representatives will be developing a national science policy on the use of genetic modification technologies in the next few years. As citizens, we’ll be asked to vote on the use of these technologies. What factors do we want policy makers to keep in mind as they decide the future of genetic engineering? There are several policy options to consider:

Banning - Should we ban it? The use of this technology is currently not prohibited in the US, Russia, and China. While many countries are currently considering legislation that would ban genetic modification of children, it has been fully banned in 44 countries around the world, including Germany, France, Italy, Australia, Canada, Brazil, Costa Rica and Japan.

Regulating - Should we regulate the technology to allow only certain applications? Many believe there may be acceptable uses of genetic modification in the future, but want to be sure that appropriate limitations are set, through government or other oversight, to ensure safe and ethical use. Should we regulate any proposed form of genetic engineering if, when widespread, it has a harmful effect on individuals and society? If so, who determines what that threshold is?

Promoting – Should we promote the widespread use of this technology? Some believe that genetic modification holds tremendous promise for preventing genetic diseases and that society should pursue policies to promote or encourage its use in the future, despite what other sideline “designer” applications are developed as a result.

It’s time to get the conversation going. What are your thoughts?

Finally, some good news for women at risk of HIV

Women and girls are the new face of HIV/AIDS. Globally, there are twelve HIV-positive women for every ten HIV-positive men. In the hardest hit countries of sub-Saharan Africa, young women are three times more likely than their male peers to become infected.

The disproportionate impact of HIV on women is due to a variety of biological and socioeconomic factors, factors that also make current HIV prevention tools – including condoms and mutual monogamy – inaccessible to those most at risk. For example, many women do not have the social or economic power necessary to insist on condom use and fidelity, or to abandon partnerships that put them at risk.

Thus, there is a desperate need to develop new user-controlled tools to enable women to protect themselves, such as vaginal microbicides. Over the past two years, a series of flat findings and trial closures have shaken public confidence in research to develop safe and effective microbicides. But now there’s a glimmer of hope.

Yesterday, at the 16^th Conference on Retroviruses and Opportunistic Infections in Montreal, a team of researchers funded the US National Institutes of Health announced the results of HPTN 035, a clinical trial of PRO2000 and BufferGel, two candidate vaginal microbicides.

This study enrolled over 3000 at-risk women in Malawi, South Africa, United States, Zambia and Zimbabwe. In addition to showing that these products were safe to use, the study found that women used PRO2000 (as a topically-applied gel) plus condoms had 30% fewer HIV infections than those who used only condoms or condoms plus a placebo gel.

Although the decrease in HIV infections among women using PRO2000 did not quite achieve statistical significance, this is first large-scale clinical trial showing that a candidate microbicide might actually work in women. A second trial of PRO2000, enrolling more than 9000 at-risk women in Southern Africa, is currently underway. The results of that study – known as MDP201 – will be available in November. If the data from the MDP201 trial also show that PRO2000 is safe and effective, it is expected that this gel will be submitted for regulatory review and approval, hopefully giving women worldwide access to a new and sorely needed HIV prevention tool.

Octuplets Mother Speaks Out

Nadya Suleman, mother of the recent octuplets born in California, has done her first interview with a major news outlet. (Although Suleman was seeking USD 2 million for the interview, NBC maintains that they did not pay her. However, that doesn't rule out "compensation" in other forms.)

Unfortunately, Suleman's interview has continued to raise, rather than answer, questions. Foremost among them, for me, is her claim that she had six embryos implants per IVF procedure. This... simply does not ring true. Or at least plausible, if she was using a US fertility expert.

Consider this: in order to have done so, this means Suleman would have needed to find, at age 26, a fertility doctor who would implant six embryos. ASRM guidelines are no more than 3 embryos for a woman under the age of 35, and that's if she has a history of problems with conception. With a 'clean' history, only 2 embryos are recommended. Now, it sounds like Suleman might have qualified as having difficulty conceiving, with several ectopic pregnancies and miscarriages prior to IVF. But even accounting for that, it's double the recommended standard. For each pregnancy.

But stop to do the math. While one vial of donor sperm would be more than enough for all of this, it means that they collected at least 36 eggs from Suleman, and that all of those eggs were viable enough to implant once fertilized. Realistically, not every egg retrieved is going to be mature, and not every egg is going to fertilize (unless you're using something like ICSI). Realistically, you're looking, at the very least, at 1/3rd more eggs than that being pulled out (and even that is a very, very low number - remember, they're saying that there were six viable eggs to implant per cycle. A quick web search shows that 1/3 of the eggs removed at any time are not mature, and of the ones that are mature, only half reach the point of being "good enough" to implant).

Now let's go over to CDC stats. While the last data is from 2005, which was going on 5 years ago, Suleman started her IVF course in 2001, so some of this data is specifically applicable (and some of it only extrapolation). According to the CDC, only 35% of ART cycles resulted in a pregnancy, and of those, 82% resulted in a live birth. So again, Suleman seems to have defied the odds. A lot. And as the CDC says about frozen eggs, "[b]ecause some embryos do not survive the thawing process, the percentage of thawed embryos that resulted in live births is usually lower than the percentage of transfers resulting in live births." While only 15% of embryos transferred were frozen, of those 15%, only slightly more than 1/4 ended up in live births.

Again, the odds make this seem incredibly unlikely.

Finally, fertility clinics are required by law to report their ART data, under the Fertility Clinic Success Rate and Certification Act. This gives us a decent way of tracking ART results - and also who is doing ART. In 2005, eleven clinics in California did not report their ART data (which would include embryo transfers/live birth data/etc). Of those eleven places, it looks like seven were within an hour of her home (keeping in mind her back injury likely limited the distance she could travel). Of the clinics that did report their data, 35 are within an hour of Whittier, California. However, given these clinics are compliant with reporting their data, it seems safe to eliminate them from immediate suspicion. (As for the potential Mexcio connection, Tijuana is approximately two hours away. Certainly not out of the question; an hour was a random number drawn from thin air. Suleman has certainly shown herself to be willing to go to significant length, and pain, to achieve her goals.)

All in all, what does this mean? Not much. Over 300 pages of records on Suleman have been released to the press, under a public records request to California's Division of Workers' Compensation. While it doesn't appear that the fertility clinic (or doctor) that treated her is in those records, there is ample evidence to support that she did have problems conceiving, and that she had known psychiatric issues, including what was diagnosed as either postpartum depression or PTSD. Issues that should have limited, if not prevented, future implantations.

Ultimately, until Suleman names her doctor, or said doctor speaks out, little will be conclusively known. But the facts remain simple: the facts do not add up.
-Kelly Hills

More on the Octuplets

Our friend and supporter, Art Caplan, sheds some more light on the ethical implications of the octuplets in his Philly op-ed:

"Something has gone terribly wrong when a 33-year-old single woman - who has no home of her own, no job, and a mother who worries her daughter is "obsessed" with having children - winds up with 14 of them. And all are under age 8, including eight newborn babies now in a neonatal nursery in various states of prematurity.
Examining what exactly went wrong may shed some light on what ought to be done. If doctors cannot prevent such a shambles from recurring, then society must.

The woman in question, Nadya Suleman, lives with her parents in a small home near Los Angeles. She has had infertility problems linked to blocked Fallopian tubes. She can make eggs, but they cannot be fertilized naturally because of the blockage.

Suleman apparently used donated sperm and in vitro fertilization to create all the embryos that became her children. She underwent treatment to cause her to produce many more eggs than the normal one per month, and they were surgically removed from her body and fertilized in lab dishes. Some of the resulting embryos were put back into her body, and that is how her first six children were made.

Unhappy with only six, Suleman sought further fertility treatment and had an additional eight of her embryos defrosted and implanted. They produced the now famous octuplets who, after a Caesarean section, are in intensive care at Kaiser Permanente Medical Center in Bellflower, Calif. Sadly, there is no known case of octuplets in which all escaped severe disabilities.

The most obvious questions raised by this sad saga include: How did Nadya Suleman become a fertility patient? And how did she get eight embryos implanted when she already had six young children to care for in a tiny house, with no partner and no income?
Some fertility doctors would answer that it's not their job to decide how many children a person can have. Jeffrey Steinberg, medical director of the Fertility Institutes, which has clinics in Los Angeles, Las Vegas and New York City, was quoted as saying: "Who am I to say that six is the limit? There are people who like to have big families."

James Grifo, a renowned fertility specialist at New York University, had little time for those wondering why Suleman was a patient. "I don't think it's our job to tell them how many babies they're allowed to have," he reportedly said. "I am not a policeman for reproduction in the United States."

With all due respect, the idea that doctors should not set limits on who can use reproductive technology to make babies is ethically bonkers.

If someone comes to a clinic with a history of child abuse, active drug addiction, and a rap sheet with serious felonies, should the doctor simply say: "If you have the money, I will make all the babies you want"? That gives cash and carry a whole new meaning.

Doctors have an obligation to consider patients' requests for treatment, but they do not have to honor them. One very good reason not to do so is if a doctor believes that what the patient wants would put children at grave risk.

Putting eight embryos into a woman is exactly that - putting kids at grave risk. Putting eight babies into the family of a single mom already trying to cope with six other young kids, with no money and little help, is putting kids at grave risk. The doctors who allowed Nadya Suleman to receive multiple embryos engaged in grossly unethical conduct.

The other major ethical problem raised by this story is the hijacking of health-care dollars by someone acting irresponsibly.

Suleman had to know that starting a pregnancy that might create eight tiny lives was to risk killing herself, as well as killing or severely disabling one or more of the babies. Fortunately, she made it through the pregnancy. But the cost of neonatal care for her eight new children probably will exceed $1 million.

When they are discharged from intensive care, more millions of dollars in medical costs likely await, not to mention the help Suleman will need just to handle all of her children's basic needs.

Society needs to discourage mega-multiple births. And it is clear what needs to be done to accomplish that.

If the medical profession is unwilling or unable to police its own, then government needs to get involved. We already have rules governing who can get involved with adoption and foster care. Shouldn't these minimal requirements be extended to fertility treatment? And shouldn't some limit be set on how many embryos can be implanted at one time, along with some rules about what to do with embryos that no one wants to use?

Other nations, such as Britain, keep a regulatory eye on reproductive technologies and those who wish to use them, knowing their use can put kids at risk in ways that nature never envisioned. We owe the same to children born here."

Original article here.

Nigerian Families' Claims Against Pfizer Over Drug Tests Reinstated

[Courtesy of Alicia Ouellette]

The United States Court of Appeals for the Second Circuit has handed down a case of major importance in research ethics and international law. The case is Rabi Abdullahi v. Pfizer. The plaintiffs are Nigerian children and their families who were subjected to medical experimentation in Nigeria by drug manufacturer Pfizer. Specifically, the children were among two hundred sick children in Nigeria given the experimental antibiotic Trovan as part of a protocol designed to test the efficacy of Trovan against that of a standard antibiotic treatment. The plaintiffs sought, and won, the right to sue Pfizer in federal court for damages caused by Pfizer's involuntary medical experimentation.

The decision is legally significant for its holding that nonconsensual experimentation on humans violates a legally enforceable norm of customary international law. No American court or treaty recognized such a norm before this case. Not surprisingly, the opinion is not unanimous. The dissent accuses the majority of creating "a new norm out of whole cloth [that] misconstrues – rather than vindicates – customary international law."

The opinion can be accessed at this link: http://www.ca2.uscourts.gov:8080/isysnative/RDpcT3BpbnNcT1BOXDA1LTQ4NjMtY3Zfb3BuLnBkZg==/05-4863-cv_opn.pdf#xml=http://www.ca2.uscourts.gov:8080/isysquery/irla125/10/hilite.

The opinion is long, and includes several technical legal issues. But the court's analysis of whether universally accepted and legally enforceable norms of international law prohibit medical experimentation on non-consenting human subjects (which begins in earnest at page 22 of the opinion) breaks new ground in American law. It is worth reading.

[Editor's Note: For articles that give you more background on the Nigeria vs Pfizer Trovan suits, here are links to few:

http://news.bbc.co.uk/2/hi/africa/6721771.stm

http://news.bbc.co.uk/2/hi/africa/1220032.stm

http://news.bbc.co.uk/2/hi/africa/6719141.stm

http://www.washingtonpost.com/wp-srv/world/documents/Clinical_Trial_Report.pdf

http://www.washingtonpost.com/wp-dyn/content/article/2006/05/06/AR2006050601338.html]

Water Fluoridation in Burlington

Greetings all.

Tonight, here in Burlington, VT the water fluoridation issue took the main stage at the first televised mayoral debate. For several minutes the mayoral candidates responded to a question asked by SwabVT.org co-founder, Geoff Golder.

The Question:

"The American Dental Association recommends that children under the age of twelve months not consume fluoridated drinking water, and both the State Department of Health and the Burlington Board of Health concur with this stance. The Burlington Board of Health recently recommended to the City Council that the city take a precautionary stance towards community water fluoridation by discontinuing the practice. What would you do to ensure safe drinking water for the children of Burlington, considering that our city's water is fluoridated?"

Unfortunately I was preparing coffee in the next room and did not hear the question actually being asked. In between bean-grindings I heard the word "fluoride" come from the living room. Yes, Kurt Wright, the republican mayoral hopeful, was talking about fluoride. He noted that seventy-five percent of voters voted to keep fluoride in the water in 2006. The beans mostly landed on the kitchen floor as I wasted no time in planting myself in front of the live internet stream.

Incumbent candidate Bob Kiss responded next. He noted that the ADA had issued a statement saying that children under the age of one year should not drink tap water. He also noted the concern about kidney patients. In his kind and thoughtful manner, he acknowledged the board of health decision, and recognized that it was deserved of further attention.

The final candidate, Andy Montroll, responded with what I thought was a very fair story. He mentioned that one of his children was virtually free of cavities while his other has had seven fillings. They've grown up with fluoridated water. He admittd that many people that he knows and respects, formerly convinced him that fluoridation was safe and effective, however, he also noted that he's spoken with more and more people that he knows and respects who are begining to call it into question. He emphasized that there is an answer in the science.

I regret not having been able to see one of the candidates, Dan Smith, respond to the question. I will have to pull it up on CCTV.org once they've posted it.

I think what we've seen tonight is a milestone. "Anti-fluoridationists" as they have been called, seem to be gaining more recognition and "membership" based on new science and new information. With the ADA now recommending that parents use water with no or low fluoride levels when mixing infant formula, many parents are starting to realize that this means no tap water for their kids. Yes, your kids! The National Kidney Foundation has discontinued its support of community water fluoridation and is calling for kidney patients to be "notified of the risks of fluoride exposure" kidney patients will undoubtedly be the next to start raising their hands and saying "what about us?" Yes, what about them? If water fluoridation does reduce tooth-decay by about 15% is it worth the risk? Is it worth forcing parents to purchase bottled water just to avoid exposing their infants to systemic fluoride? Is it worth forcing kidney patients to drink and internalize something they may be unable to process? Why not focus on providing more effective dental solutions to those who need it rather than sending a medicine through the water pipes to everyone, regardless of their condition. I bet we could reduce toothdecay even more than 15% with a more targetted and effective approach.

I believe we are starting to see that the "anti-fluoridationists" we may have thought to be quacky or paranoid, are for the most part, raising concerns that we all share. (for the most part I said!) They are concerned mothers. They are the concerned friends and family of kidney patients. They are people who are involved with healthy living. They are the people who don't want anything special in their water.

The next time you hear some wacky anti-fluoridationist in the news, give him or her a listen. If you're concerned with ethics and justice, I bet you're an anti-fluoridationist, yourself, and never even knew it.

Best Wishes,
Kevin Hurley

Interacting with the Experts

Every so often, you get a really fun opportunity to interact with experts in a field at a casual level. I've had the pleasure of having several of these random moments, and one of my first involved neuroethics, an article by Danniell Dennett, the 2005 National Undergraduate Bioethics Conference, and some professor by the name of Paul Root Wolpe. Of course, it wasn't until later that I realized precisely who Dr. Wolpe was, at which point I promptly suffered from extreme mortification at my casual level of arguing - but I think that's half the fun of those hindsight situations.

I had the privilege of getting to know and occasionally work with Dr. Wolpe after that first random meeting, and my impression of him hasn't changed. He's extremely fun to talk to about a wide range of subjects, still has the coolest job title in bioethics (Chief Bioethicist of NASA!), and recently became the Asa Griggs Candler Professor of Bioethics and Director of the Center for Ethics at Emory University. And maybe most importantly, Dr. Wolpe will still take the time to sit down and chat with someone interested in the field, even if they're a young and nervous undergraduate with more chutzpah than common sense.

Today, you don't need a random encounter to interact with Dr. Wolpe. He's hosting USA Today's Faith and Reason Forum, and will be popping online through-out the day to answer questions about all sorts of bioethical issues. The topic they're starting out with is predictable: a discussion of Nadya Suleman's decision to carry octuplets to term, and the wide range of ethical implications behind that decision.

So if you have time, pop on over and join the discussion. It's bound to be entertaining and educational.

And if you are lucky enough to live near the University of Maryland, Baltimore County, check out Dr. Wolpe's lecture on "Bioethics in Space: Thorny Ethical Issues at NASA". It's on April 29th, hosted by the UMBC Bioethics Student Association (led by our very own intrepid Dr. Andrea Kalfoglou), and directions and other details are on the website. But if you can say "bioethics in space" without hearing Muppets, you're a better person than me.
-Kelly Hills

Reproductive Autonomy Runs Amok

In a follow-up post to Kelly's previous post, it seems that Nadya Suleman's use of IVF technology is clear misuse and abuse of ARTs (Assisted Reproductive Technologies). The doctor who implanted the embryos should be investigated, because in helping this woman become pregnant with 8 children, he or she violated one of the basic tenets of medicine -- "Do No Harm". Hopefully, the Board of Medical Licensure will investigate and determine what the possible motivation was for this doctor's actions, whether it was a one time lapse in judgment due to extreme personal difficulties, or if it represents a small part of a larger pattern of unethical behavior and practice for the doctor and the fertility clinic.

There are multiple ethical considerations at play when an IVF specialist is approached by any woman and a 'burden vs benefit' analysis is employed. When someone who has already had six children through the procedure seeks more, I cannot imagine a valid or justifiable benefit -- the burdens include physical and financial costs to the mother (who has already declared bankruptcy), to the grandmother, to the siblings, to the children born, and to society. And while one might argue that this is an exercise in reproductive autonomy, we, as a society need to ask 'how far does reproductive autonomy go?' Does it include the right to create children who been disabled or dis-enhanced? (A nightmare scenario vaguely reminiscent of Dean Koontz' novel, One Door Away from Heaven). How we answer this question will have an impact on how we deal with future cases, such as those involving genetic engineering.

Hopefully, this case will call attention to the need for regulation and oversight of Assisted Reproductive Technologies. Currently, we have a laissez-faire attitude towards ARTs and fertility clinics; we have trusted the doctors and clinics to regulate themselves, via the American Society for Reproductive Medicine --and this case demonstrates that we can no longer simply turn a blind eye.

How Many is Too Many?

Unless you've been hiding under a rock this last week, you're aware of the octuplets born to California single mom Nadya Suleman, and the intense ethical debate surrounding her pregnancy. Even before it was revealed that she has six other children (apparently all from IVF, although details are a bit fuzzy), medical experts were ready to lynch the IVF specialist who implanted that many embryos into Ms. Suleman. And since then, the information that has come out has been more and more dismaying. The problem is, much of the information coming out is still speculation, and few solid facts are known. This makes it difficult to do more than speculate and contribute to the signal to noise ratio, which at the moment is definitely loudly on the side of noise.

So rather than continue to discuss the particulars of Ms. Suleman's case, which will have to be dissected in its own due time, I want to open to forum to a related question that has been repeated in the discussion of her story: how many children is too many children? Not how many implanted embryos is too many embryos, but at what point (if any) do fertility doctors say sorry, no more kids? Should Ms. Suleman have had any embryos implanted at all, given her six other children? Or is the ability to pay for IVF the only thing that should be considered? Should the financial state of the individual or couple be considered? Job? Income? What factors should go into deciding whether to treat for infertility via IVF? And should the "how many is too many" question be posed to adoptions, as well (Angelina Jolie and Brad Pitt clearly coming to mind)?

Or put another way: is the problem with the birth of the octuplets the fact that they were born all at once, and if Ms. Suleman had continued to quietly have eight more children via IVF, no one would have said a thing?

It seems like this single question - if an outside source is utilized to have children, is there a point at which it can be determined that the person has too many children to have more - is fraught with the potential of paternalism and of violating the choice of family construction.

I don't even begin to have an answer to this; I doubt I've even begun to tease out all of the potential questions wrapped in what is an incredibly thorny issue. But let's open it to debate - what do you think?
-Kelly Hills