David's First Book Review: The Immortal Life of Henrietta Lacks

I've discovered reading again.  Or maybe what I've done is made a conscious decision to set aside time to read.  Some books I've recently read have nothing to do with cancer, like Cloud Atlas.  Then there's The Immortal Life of Henrietta Lacks.

Rebecca Skloot did a marvelous job telling the story of Henrietta Lacks, a woman from Baltimore whose cervical cancer cells became the very first immortalized cell line.  I think this book is a "must read" for anyone engaged in cancer research, if for no other reason than it reminds us that every cell line we work with was once a tumor growing in an individual... a person who had a family and friends, a person who suffered and probably died of cancer.  Each of these people has a story, and knowing that story can inspire us to work harder to find better treatments with fewer side effects.

But aside from the human interest angle, the book is an interesting study in the evolution of medical ethics.  When Mrs. Lacks was treated, in 1951, there was nothing "unethical" about taking some of the cells that were removed from her during the course of her treatment and trying to grow them in the lab.  She did not give informed consent for her cells to be cultured, but the very concept was not a part of medical research at the time.

Times have changed.  Just last week I was getting informed consent from a woman one of whose children was going to donate bone marrow to another.  Our cancer center has a "leukemia bank," a freezer full of bone marrow removed from patients with leukemia, frozen away for future research.  As I explained to her, it can be hard to tell what is abnormal about the leukemia cells if we don't have normal cells to compare them to.  So we ask each normal bone marrow donor to allow us to freeze a teaspoon or so of marrow for comparison studies.  In order to do this, we have to get approval from an Institutional Review Board and the donor (or the donor's guardian, in the case of a minor) has to sign a statement asserting that he or she consents to having this normal marrow stored away.

And that is just to STORE the marrow.  If we want to use the marrow for research, we have to get approval from the Institutional Review Board for the research project and use the marrow anonymously.  If we need clinical information about the marrow donor (or the leukemia donor), we need to either track that person down and get informed consent for the specific experiment or we have to convince the Institutional Review Board that doing so would be an undue burden (if, for example, the patient has subsequently died or has left no contact information or the study will involved hundreds of samples and the data will be used anonymously).

None of these safeguards were in place in the 1950's.

Another fascinating question raised by Ms. Skloot is the question of intellectual property and a patient's rights to his or her own tumor.  Ms. Skloot contrasts Mrs. Lacks, whose family received nothing in exchange for her cells (although, to be fair, neither Johns Hopkins nor Dr. Gey, the man who cultured her cells, received any money for her cells, either.... they were distributed freely to any interested lab anywhere in the world), with Ted Slavin and John Moore.  Mr. Slavin was a man with hemophilia who sold his serum because it had extremely high levels of antibody against Hepatitis B and then supplied serum to Baruch Blumberg, a virologist who discovered the link between Hepatitis B and liver cancer and created the first vaccine against Hepatitis B.  Mr. Moore's spleen was removed as treatment for Hairy Cell Leukemia, and his physician grew a cell line from the spleen, which he then patented and licensed to biotechnology companies to "commercially develop."  In each of these cases, something of value was taken from a patient, sometimes with their knowledge and consent, sometimes not.  In each case, the material contributed to the development of the nascent biotechnology industry, eventually being used to generate profit.

I would love to hear my readers' thoughts on the ethics of these situations.  After all, it seems wrong for someone to profit from cells taken from my body, but the cells are not inherently valuable... it's how they are used that is valuable.  Without intellectual input from a scientist, they are just cells.  But does this mean that, as the California Supreme Court ruled, I don't have any right to profits generated from tissues removed from my body?

One final note:  Ms. Skloot speaks eloquently about how Mrs. Lacks was treated by Johns Hopkins (and subsequently seemingly forgotten).  Just recently, the Johns Hopkins Urban Health Institute announced the Henrietta Lacks Award for Community-University Collaboration, a prize of $15,000 to a community entity that collaborates with Hopkins to work to improve the health and well-being of the residents of the City of Baltimore.

Thanks to Ms. Skloot, Van Smith, and Mike Rogers (all of whom have written about her), Henrietta Lacks will achieve some level of immortality beyond the HeLa cell.

Photo Credit

Another Ethical Dilemma

The ethics of modern medicine has always fascinated me, and Pediatric Oncology has provided me with more than my fair share of ethical issues to contemplate. I want to share today’s, and see what people think about this particular, emotionally charged, situation.


I received an email today from a colleague in another state. He trained under me, and I guess he thinks I did a good job, since he emails me for advice from time to time. He met a new patient today – a 23 year old woman with a new diagnosis of osteosarcoma. Unfortunately, she is 20 weeks pregnant.

One of the mainstays of osteosarcoma treatment is high dose methotrexate. Methotrexate is a very effective drug for terminating pregnancies, and this is where the ethical dilemma begins. The patient has a choice to continue her pregnancy or not. Except that the state in which she lives does not allow medical assistance funds to be used to terminate a pregnancy, and she has Medicaid as her sole source of health insurance. She cannot afford to pay for an abortion herself. If she chooses to continue the pregnancy, either out of necessity or out of desire to do so, giving her methotrexate will be fatal to the baby inside of her.

If the patient chooses to remain pregnant, my friend has some very difficult decisions to make: should he wait to treat her until the baby is born? This would give the tumor as much as 4 months to spread before treatment, a huge risk to the patient. Should he begin therapy early, maybe once the third trimester begins, and just not use methotrexate? This would allow the baby to develop to full term prior to delivery, and only delay beginning chemotherapy a few weeks, but would provide less than optimal care to his patient. Could an obstetrician ethically deliver the baby early, say at 30 weeks, a time when the child’s development is likely to be normal (but, of course, may not be) despite being premature? This would allow him to use methotrexate almost 3 months earlier than if the baby is delivered at full term.

I told him what I think I would do, but I’m glad that for me this is just an ethical puzzle, instead of a real situation where I have to make real decisions.

Related Posts:

The Irony of Patient Autonomy
Thank Goodness for Ethics Committees

How Small a Chance Is Too Small?

I’ve written about difficult cases before, but this case is really eating at me. It touches on issues of patient autonomy and how much influence we, as physicians, have over our patients. But the real issue is one of futility. How small a chance at survival is too small to offer a very toxic treatment?

The patient is a young boy with leukemia. We have been treating him for over a year, and his leukemia just won’t go into remission. For the past 3 months he has been in the hospital, first to receive chemotherapy and then to manage the side effects we caused. His bone marrow is nearly empty, but almost 80% of what few cells are present are leukemia cells. His only potential curative therapy is a bone marrow transplant.

Therein lies the problem. Not only does he have refractory leukemia, but his lungs are significantly injured from his previous chemotherapy, functioning at just about 55% of their predicted ability. For my patient, this is a major problem, because sick lungs make a bone marrow transplant very risky. Also, he doesn’t have a matched donor, so we would have to do a highly experimental type of transplant called a “reduced intensity haploidentical transplant.” This means we would give less than the usual amount of chemotherapy (to try to decrease the toxicity), and would use a donor that is only half matched.

I presented this case to the adult BMT group last week. Not one of them thought going through with the transplant was a good idea. They are convinced the patient will do badly, that he will end up dying in the ICU on a ventilator, and would never be cured with this approach anyway. Better to send him home on hospice care.

I polled a number of pediatric colleagues by email. They all said the same thing – better to do hospice care than a transplant that will most likely make the patient sicker before he dies anyway.

Our group has discussed the case extensively. We all agree that the chance of cure for this child is less than 5%. There is a 95% chance he will die faster and in more pain if we go ahead with the transplant than if we send him home on hospice care. So is the more humane choice to not offer the family a transplant, knowing the odds are overwhelmingly against success, knowing that the transplant will most likely make an already tragic situation worse?

Who gets to decide if the 5% chance of a cure is worth the risk? Is this chance of success so small as to qualify as futile?

If I know the father the way I think I do, if I hold out ANY chance of cure, he’ll take it, no matter the cost. That means, if I offer the family the transplant, he will go for it. But is that fair of me? He doesn’t know what it’s like to watch a child die in the ICU. I don’t think I can fully explain to him how awful a death his son may have, especially compared with what it would be like for him to die peacefully at home. Given that, can he truly give informed consent?

On the other hand, if I don’t offer the transplant, I take away even that slim chance of survival. Can I ethically do that? Or is that a decision the parents get to make?

 Photo Credit

The Irony of Patient Autonomy

One of the cornerstones of medical ethics is the concept of patient autonomy. MedicineNet.com provides a succinct definition: “The right of patients to make decisions about their medical care without their health care provider trying to influence the decision. Patient autonomy does allow for health care providers to educate the patient but does not allow the health care provider to make the decision for the patient.”

At lunch the other day, I was talking about a particularly challenging case when this concept came up. After thinking for a few minutes, I was struck by a sense of irony that I wanted to share in case others have thoughts about this.

The patient is a teenager with leukemia. When she was diagnosed with leukemia, we didn’t really give her parents any choices about treatment. We told them their daughter has leukemia, she needs chemotherapy, and we think she should get this particular regimen. Sure we received informed consent to treat the patient (whether this is truly informed consent is a topic for a future post), but it’s not like we gave the parents a choice of regimens or the option to forego chemotherapy. And because leukemia in children is curable, even if the parents had refused chemotherapy, we would have gone to court to force her to be treated.

Did we respect the patient’s autonomy here? Based on the definition above, I would say we did not. We certainly influenced the decision – by not giving the parents any choices.

Fast forward to last week, when a bone marrow examination revealed residual leukemia. The next course of action at this point is not clear: should she go straight to a bone marrow transplant? If so, should it be a standard transplant, or a more experimental approach? How about more chemotherapy? Is so, which regimen? The right choice is not clear. My “lunch date” is not a physician. So he asked me, “How will the family decide?” Full of respect for the patient’s autonomy, I answered, “Well, I will lay out the options, list some pros and cons, and the family will make a decision.”

This is when Marco asked the question that sparked this posting: “How will they make that decision? They don’t have the expertise to make that call, do they? Isn’t that what you are trained for?”

And that’s when it struck me. This family has had two key decision points: the day the girl was diagnosed, and the day her marrow showed persistent leukemia. At the first point, my expertise was unimportant… any oncologist would have said the same thing (that she needed chemotherapy), and the patient’s autonomy was only a secondary consideration. At the second point, when the optimal choice is NOT clear, when the decision should be MOST informed by someone experienced, that’s when I was explicit about my desire to lay out choices and let the family decide.

I still don’t think I should tell the family what decision to make… I just think it’s ironic that when the decisions are more complex, and my expertise matters more, the patient’s autonomy is even more important.

Maybe that’s how it should be. What do you think?

Therapeutic Cloning Takes A Big Step Forward

Leber’s Hereditary Optic Neuropathy
Leigh Syndrome
Myoneurogenic Gastrointestinal Encephalopathy

What do these disorders have in common? They are all mitochondrial diseases.



What is a mitochondrial disease? Mitochondria are the parts of a cell that are responsible for generating energy. Mitochondria contain DNA, just like the nucleus does. Mutations in mitochondrial DNA can cause them not to function correctly, and some of these mutations cause the diseases listed above (and others).

When a baby is conceived, we think of the baby’s DNA as coming half from the mother and half from the father. That is true for the DNA in the nucleus, but not true for mitochondrial DNA. All mitochondrial DNA is inherited from your mother.

As a side note, the fact that all mitochondrial DNA is inherited from the mother is the basis for anthropological studies that allow scientists to trace the origins of humanity back to “Mitochondrial Eve” in Africa.


Since all mitochondrial DNA is inherited from the mother, replacing mitochondrial DNA that carries a disease-causing mutation with mitochondrial DNA from another source would prevent a woman from passing on such a disease to her children.

That is the basis for the work by Shoukhrat Mitalipov’s group at the Oregon Health and Science University published online in Nature on August 26. This group took an egg from a female monkey and removed the nucleus, replacing it with the nucleus from a different female. This hybrid egg, with nuclear DNA from one female and mitochondrial DNA from another female, was fertilized, and the resulting embryo was allowed to develop. Not every embryo developed normally, but some developed into seemingly normal monkeys like the ones shown above.

This approach would allow a couple with a family history of mitochondrial disease on the mother’s side to have children with mitochondria donated by an unrelated woman, and they could have children with no risk of developing the disease.

The monkeys described in the paper have genetic contributions from 3 adults. Does that mean there are three parents? I guess that depends on how you define “parent.” If you are a parent simply by virtue of having contributed DNA to a child, then yes, these monkeys have 3 parents. Of course, if a parent is defined as the adults who raise you, then a child conceived in this way would have 2 parents. The ones who raise the child.

Experiments like these raise huge ethical issues. Therapeutic cloning like this introduces changes directly into the germline (the DNA that is passed from parent to offspring), something that has long been taboo in the mainstream scientific community. It also raises interesting custody issues (does the donor of the mitochondrial DNA have any parental rights?). I’d be interested to hear what people think about this.

Like it or not, we are on the verge of a new era of genetic medicine. Some aspects of genetic medicine will not be controversial (tailoring medical treatments based on the presence of specific mutations), but other aspects are sure to raise questions (like the experiments described in this paper). It is critical that we begin to have serious, society-wide discussions about these issues, before it is too late and the discussions become arguments.

Related Posts:

Cancer Stem Cells and Familial Cancer Risk for Breast Cancer

Stem Cells, or "A Rose By Any Other Name..."

Thank Goodness for Ethics Committees

(Blogger’s Note: Due to the sensitive nature of this case, even more details than usual have been changed.)

The patient was coming to me to sign consent to donate bone marrow. Just one problem. She’s pregnant.

Does that matter?

What if I told you that the bone marrow donor is 23 years old and is donating for her sister who has leukemia?

What if I told you that the donor is 19 and is donating for an unrelated child with severe combined immune deficiency syndrome (SCIDS)?

What if I told you that the donor is 17 and is donating for her father, who has lymphoma?

There are so many variables that play into the answer to the first question I posed: Does it matter? Certainly if she is pregnant and undergoes general anesthesia, she exposes her unborn child to a small but measurable risk. How about regional anesthesia? How about the blood loss associated with marrow donation? Bone marrow transplant for a child or young adult with certain types of leukemia can be considered standard of care. What if the transplant is experimental, rather than standard?

Although these questions may seem abstract, they are not. In fact, one of the situations above happened to me recently. It was the kind of situation that made me happy that our hospital has an ethics committee.

Related Posts:
When the "routine" is anything but
A Day in the Life of a Pediatric Oncologist

Access to Experimental Drugs for Dying Patients

Before I went to the ASCO meeting, I read a fascinating interview conducted by Dr. Val. She interviewed Dr. Emil J. Freireich, the director of the Adult Leukemia Research Program at M.D. Anderson Cancer Center. The discussion took place at a press conference announcing the introduction of the Access, Compassion, Care and Ethics for Seriously Ill Patients Act, which seeks to increase terminally ill patients’ access to promising investigational drugs. Dr. Freireich made some excellent points about the risk-averse nature of the FDA’s drug approval process, and how this process slows the development of new drugs.

Dr. Freireich’s interview made me think more about the process of experimental drug approvals, and the pros and cons of allowing patients access to investigational drugs before they are proven safe.

One interesting point Dr. Freireich made is that, unlike any other scientific research, research on new drugs requires government approval before it even starts. If I want to research the mechanism by which a cancer-related gene contributes to the growth of a sarcoma, I don’t need anyone’s permission to begin the experiments. I just do them. On the other hand, if I want to test a new cancer drug, I not only need the approval of the hospital’s Institutional Review Board (which is charged with protecting patients from unethical medical research), but I also need the approval of the federal government, in the form of the FDA.

Why is this important? Well, the folks who decide which drugs get to be tested are rarely physicians. So they often lack the expertise to appropriately judge the degree of risk posed by a new drug against the risks faced by the patient.

What do I mean by that? I’ll give you an example from my own career. I have been conducting research using a drug called samarium-153-EDTMP for patients with high risk osteosarcoma. This drug works by delivering radiation through the blood stream to places where the osteosarcoma is involving bone. The FDA approved my research, but did not allow me to treat anyone under the age of 13. Why this restriction? Because the drug also delivers radiation to growth plates, the parts of bones where growth occurs. There is a concern that growth plates might be damaged, and if I treat growing kids, they may stop growing. I argued, quite vigorously, that these are kids who are all destined to die of their disease… they represent the osteosarcoma patients with the worst prognosis, and very few are cured. So, to deny them access to a drug that could help, because it may stunt their growth seems… absurd. I lost the argument, though, and all subjects on the study are 13 or older. M, who came to me from Japan for treatment, was not allowed on the study because he was 12. He died several months later.

So why not let terminally ill patients take whatever drug they want? Why limit access at all? Some might argue exactly this point, saying that if the patient is going to die anyway, why not let him/her take whatever they choose. Well, what if an experimental drug hastens death or increases suffering? If a patient has a good quality of life, and an unscrupulous person offers an experimental drug that is not only ineffective but hastens death, depriving the patient of time that could have been spent with friends and loved ones enjoying life, that’s a problem. Or what if the drug is not only ineffective, but causes horrible and unmanageable side effects without hastening death? Surely that is also a bad outcome. Of course, what if the drugs extend the patient’s life with minimal side effects? Shouldn’t patients be allowed to make that gamble even if there isn’t enough research supporting this possibility?

And aren’t there other benefits from “trying everything” beyond extending life? For example, my patient M enrolled on a Phase I study. In my post about his family’s decision making, I mentioned that only 3% of patients in Phase I studies experience any benefit, but then talked about how benefit can mean so much more than “the tumor got smaller.” Benefit can mean feeling at peace with a decision, and feeling a sense of closure. These are real benefits that patients can get from investigational drugs, even if their tumors don’t shrink.

These are issues that come up in my practice all the time. When standard treatments no longer hold any hope of cure for my patients (who are all children or young adults), they and their families become desperate for something, anything, to try. I know how hard it is to say “No” to someone like that, especially someone I’ve treated for years and to whom I have grown very close. But I also know that I vowed to “Do no harm.” And that means making sure that I’m not just pulling something off the shelf to “give something.” Of course, I suggest as much as I can… as much as makes sense and has some scientific backing. I’ve certainly treated patients “off label” (using an FDA approved drug for a different indication) when it has made sense to do so.

So what’s the answer? This is undoubtedly a controversial subject, and a fertile topic for discussion when it comes to medical ethics, so there is no easy answer.

But certainly the drug approval process has to speed up. Between 1948 and 2002, there were 120 new cancer therapies approved by the FDA, but of these only 15 have any pediatric information in their approved product labeling at all. None were specifically approved for use in children. However, drug development is not without risk, and there are worse things than dying. Hopefully, someone will come up with a good solution, balancing a recognition that drug development (especially to treat cancer) requires risk with appropriate safeguards for these very vulnerable patients.

An advertisement campaign that promotes skin cancer

"Go get a tan. Your body will thank you… indoor tanning beds are a great way to get a healthy dose of vitamin D (and a tan, while you’re at it).”

So says the Indoor Tanning Association.

Defying established medical knowledge and common sense, the Indoor Tanning Association is claiming that UVA ultraviolet rays do not cause melanoma.

This kind of outrageous claim by a pro-tanning organization would usually be easy to ignore – but unfortunately they are getting quite a bit of attention. Today they published this full page ad (.pdf file) in the New York Times, where they brazenly claim ‘…there is no compelling scientific evidence that tanning causes melanoma’ and imply that campaigns to promote skin cancer prevention through avoidance of tanning are all ‘hype’.

According to ABC News, this morning Sarah Longwell (a spokesperson for the organization) told Good Morning America that “there is nothing dangerous about getting a tan.”

Unfortunately all of this is rubbish.

Now, it is true that sunlight is important to help your body to produce vitamin D. However, since the advent of vitamin D fortification of foods, the typical American diet contains plenty of vitamin D already, and rickets (vitamin D deficiency) has become rare in this country.

Courtesy MedicaLook.com

The ultraviolet rays in sunlight, however, are thought to be a major cause of melanoma, the most deadly form of skin cancer. This article provides a nice overview of the topic, including describing the ability of UVA to directly damage DNA.

Since summer is coming, I’d suggest that if you’d like the tanned look without the risk, there are sunless tanning alternatives you can look into. No matter your skin type, the American Academy of Dermatology recommends daily use of a sunscreen with an SPF of 15 or greater. Further information about skin cancer, including the ABCDs of melanoma, can be found here.


Courtesy, Philip A Bryant Melanoma Foundation

Or as Dr Benabio puts it: “Your natural skin color, even if ‘pasty’ is beautiful.”

In sum, the International Tanning Association's ad campaign is irresponsible and dangerous. I'm not sure I can say it enough. Please don’t allow your desire for a tan to put you at risk for a preventable cancer.

Some helpful resources:
SkinCancerNet’s article on skin cancer prevention
The ABCDs of melanoma detection
NCI’s free booklet on melanoma (.pdf)