Stem Cell Tourism Prepares for Take-off

Netta Ahituv
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Netta Ahituv

In 2004, during the first semester of his M.B.A. at Harvard Business School, Avichai Kremer felt that his right hand was steadily weakening. Eight months later he was diagnosed with the incurable atrophic disease ALS ‏(Amyotrophic Lateral Sclerosis, or “Lou Gehrig’s disease”‏), which damages the connections between nerve cells and muscles and causes a slow loss of motor abilities − until the patient dies.

“I was in shock when I received the diagnosis,” says Kremer today. “I was 29 years old. The doctor explained to me that I would die within three to five years, but first I would become totally paralyzed and lose the ability to talk, eat and, in the end, breathe. The brain remains lucid throughout and the patient is aware of what is happening, what he has lost and his inevitable end. A death sentence with no crime, no appeal and no cure.”

The interview with Kremer takes place online, because at this stage of the disease – eight years after the diagnosis – he has lost his ability to speak. He uses a wheelchair and communicates with the world by means of a computer, on which he types using head movements. “Before the diagnosis my life was wonderful: I had a girlfriend I loved, I would play basketball and train in a fitness room, I dreamed of being the CEO of a big company, marrying and being a father. I was on the way to realizing my dream.”

Although Kremer lost the ability to fulfill many of his dreams, he has not lost his knack for entrepreneurship and his persuasive talents. Two years after discovering he was ill, he established Prize4Life, a nonprofit that gives monetary awards to organizations or companies working on a cure for ALS. As part of his effort to encourage medical research, Kremer has also been exposed to numerous studies that include the use of stem cells to treat various illnesses. Stem cells are cells that have yet to be differentiated into the type of tissue they will become. In other words, they have not yet been transformed into one of the types of cells in the body − blood cells, skin cells, retina cells, and so on.

Recently, Kremer participated – along with 14 other patients – in a clinical trial of stem cell treatment for ALS patients. This was the first such trial conducted by the Israeli research firm BrainStorm, which develops medications from stem cells. “What is there to lose with ALS? In any case it’s a death sentence,” Kremer says when asked if he was afraid to participate in the innovative experiment.

Food additives to create stem cells

In the experiment, a sampling of bone marrow was taken from the patients, from which stem cells were produced in the laboratory and then multiplied and differentiated into cells that secrete a substance that causes renewed communication between nerve and muscle. The cells were injected into one of two areas in the patient’s body − either the muscles or the spinal fluid − and a follow-up of the body’s reaction began.
“First of all, the treatment was proven to be safe; no side effects were observed among the patients,” says BrainStorm CEO Adrian Harel, describing their main achievement and the purpose of the experiment. “Most of the patients showed a slight improvement in their physical condition, but in order to get a more reliable confirmation, we have to conduct the second stage of the clinical trial.”

The second stage will take place in a few months in Boston, in cooperation with two university hospitals and with 24 patients participating. Half of them will receive the actual treatment, half a placebo. Neither patients nor doctors will know who received what. The effectiveness of the treatment will be determined based on follow-up of the patients and a comparison between the two groups.

Kremer himself reports that in the short-term, he experienced an improvement in the muscle strength of his limbs and in respiratory ability. A few months later, though, the improvement disappeared. There could be many reasons for this − for example, the low dosage of stem cells administered in the experiment.

Patients like Kremer are pinning high hopes on the stem cells, as are many companies such as BrainStorm, which are diligently developing treatments that use them. Stem cell research has experienced a growth in recent years that is unprecedented in the medical field. Among doctors, researchers and patients, there is a sense that this is nothing less than a medical miracle, a solution capable of curing almost any disease.

“The enthusiasm is due to a simple reason: every field in medical research will in future be able to benefit from stem cells: brain, liver and kidney transplants; Parkinson’s; Alzheimer’s; blindness; deafness; diabetes; plastic surgery; and more. It’s a solution for a large number of different things,” explains Prof. Daniel Offen, a stem cell researcher who heads the Neuroscience Laboratory at Tel Aviv University’s Felsenstein Medical Research Center.

To illustrate recent momentum in the field, he says that six years ago 600 researchers from all over the world attended an international conference on stem cells, whereas over 4,000 researchers participated in the most recent conference two months ago.

Pharmaceutical and food additive companies are also looking at stem cells. On the shelves of pharmacies and natural food stores worldwide, one can already find food additives that are said to increase the activity of the body’s stem cells. These are substances usually produced from seaweed. The effectiveness of such additives is not entirely clear. We may reasonably assume that if they really did perform the miracles their manufacturers promise, they would be used much more widely. Whatever the case, they are also joining the worldwide stem cell craze.

“My view of these food additives is usually negative,” says Dr. Ninette Amariglio, director of the hematology laboratory at Sheba Medical Center, Tel Hashomer.

“There is no way of discussing it scientifically,” she says. “Where money is involved, everything in medicine is distorted. In the laboratory you can work on stem cells, change, multiply and differentiate them, but that isn’t done in the world of food additives.

“In my first lectures on the subject I called the industry: ‘Stem cells: The good, the bad and the ugly,’” she adds. “These cells are good and can fight the bad. Money is the ugly part. According to the solid and normative scientific information we now have, these food additives are of no medical significance.”

This year the Nobel Prize for Medicine, awarded to two scientists in the field of stem cell research, also joined the trend. Prof. Shinya Yamanaka of Japan and Prof. John Gurdon of Great Britain both succeeded, each in his own laboratory and several decades apart, to take a brilliant step that contradicted previous biological thinking.

Both went backward in terms of biological development: from a mature cell to a fetal cell. As opposed to common practice in the field of stem cells – in which it is customary to take a stem cell and turn it into a mature one – Yamanaka succeeded in changing mature cells back into stem cells. He did so in a relatively simple process, which includes the introduction of only four proteins.

Yamanaka published his research six years ago, and based his thoughts, among other things, on Gurdon’s research of 40 years ago, which proved that the differentiation of cells is reversible. “Five years ago I heard Yamanaka lecture about his discovery and I thought to myself: Either he’s crazy or he’ll receive the Nobel Prize,” says Prof. Offen. “Not only did he get a Nobel, but at the most recent stem cell conference, most of the articles presented used Yamanaka’s method. He brought about a revolution in the field.”

The great belief in stem cells has also led to the growth of a new and productive industry based on them − stem cell tourism. Many patients from the West − from the United States, Western Europe and Australia − travel to countries in East Asia or Eastern Europe for innovative stem cell treatments.
The safety and effectiveness of these treatments is not clear, but they are extremely tempting. The reason the flow of patients is from west to east is that stem cell treatments are illegal ‏(with the exception of specific clinical trials‏) in the Western countries, but legal in countries such as China, India and Malaysia. And as in many other fields, here too China leads − 86 percent of the world’s stem cell tourists come to one of the 100 hospitals in China that offer such treatments.

Reassurance from China

The following story, published in the magazine Bloomberg Businessweek in February 2007, illustrates the attractiveness of treatments in East Asia and Eastern Europe. In 2002, a 24-year-old American factory worker and father of two young children, Chuck Melton, sustained a blow to his head and suffered a severe spinal cord injury when he dived into a lake near his home. After that, he was paralyzed from the chest down. Five years after the injury, when he found no cure for his paralysis in the United States, he decided to travel to Nanshan Hospital in the city of Shenzhen, China, to receive stem cell treatment. The cost was $20,000. (Every year, about 170 foreign patients from 30 countries come to Nanshan Hospital for stem cell treatment, at an average cost of $17,000.)

The Chinese doctors injected stem cells into Melton’s spine to rehabilitate his injured cells. Melton hoped he would be able to walk again, but told the media that he would be satisfied with any improvement in his condition. Such an improvement did in fact take place a week after the treatment. The involuntary spasms in his legs ceased and, for the first time since the injury, he felt warmth in his muscles.

Another significant improvement was his renewed ability to perspire, which had been lost after the injury. This enabled him to remain out of doors longer without fear for his life. Five years on, he is unable to walk, but feels the treatment helped him, and in any case did no damage – as his American doctors had feared.

After China, the leading countries offering stem cell treatment are Russia and Ukraine, with laws that permit such treatments. Ukraine is also the home of the largest institute in the field, EmCell, which has implanted almost 6,000 stem cells in thousands of patients from 69 countries.

One of the popular services at the EmCell clinic in Kiev is treatment of HIV, in which they try to restore immune system functioning by means of stem cells. As opposed to the usual treatments administered in the West to carriers of the AIDS virus, which delay its spread, this method attempts to treat the immune system directly. Immune cells that have been damaged by the virus are “replaced” by stem cells; the treatment must be repeated every two years. The prices at EmCell vary depending on the treatment, and average $20,000.

Western researchers and doctors are strongly opposed to these clinics. They plead with their patients not to be tempted to travel to them, and even fear taking part in research or exchanging information with countries that allow them. “The phenomenon of unsupervised clinics has existed for years in many areas of medicine,” notes Prof. Reuven Or, head of the Department of Bone Marrow Transplantation and Cancer Immunotherapy at Hadassah University Hospital, Ein Karem. “It’s a phenomenon of which we have to be aware, exercise caution regarding it and warn against it. The treatments are given without having undergone all the required procedures, and therefore there is no way of knowing what the result will be.”

Offen agrees, maintaining that because there is a great deal of potential in stem cells and a possibility for profit, “in certain places they make improper and unsupervised use of them. It’s important to remember that there is a large gap between Western standards and those in the rest of the world.”

Israeli doctors are joined by their Western colleagues, and even by the International Society for Stem Cell Research, which five years ago published a warning to patients not to be tempted by unsupervised stem cell treatments.

There is another reason for this opposition, besides the concern for patients’ welfare. Prof. John Stevens, from the University of British Columbia in Canada, wrote of it recently in the Journal of Spinal Cord Medicine. He says the way in which the Chinese use stem cells for treatment will not help them to learn from it, nor will it help us or the medical community.

Stevens did not mention those whom these treatments can help − the patients. No one can expect patients to give up on the possibility of improving their condition only because this improvement will not advance the medical community. And still, the scientific community comes out against these clinics in innumerable publications and articles.

One of them, published in the journal Cell, presents a 2008 study that compared the clinics’ online advertising with the treatment they actually administer. The results of the study, conducted by an American, Prof. Darren Lau, unsurprisingly demonstrated that the clinics’ ads promise more than they actually deliver, and sweepingly ignore the risk involved in the unsupervised treatment. Another article, published in Science magazine, speaking of the boundary between medical innovation and medical negligence, adopted a more understanding approach to the stem cell clinics. While researchers see the medical innovations of the clinics in the East as a divergence from traditional treatment − which is based on orderly research − it recognized that for many patients whose time is limited, this is the only hope.

The article also noted that many scientists and physicians from the West are unaware of the fact that in the past 40 years, 80 to 90 percent of surgical techniques were not developed by the usual method of laboratory trials and clinical trials before coming on the market, but by many different routes that bypass regulation. It is particularly surprising to discover that heart transplants and laparoscopic surgery are among the treatments that skipped the customary route of approval, entering medical practice directly from the development stage.

Chinese doctors also want to defend their professional integrity. In an article published in Businessweek, Dr. Sean Hu of Nanshan Hospital said stem cell treatments in the hospital where he works are completely safe and are done only after all safety precautions have been taken. He writes that if the doctor and the hospital have had suitable training, there is no reason to be afraid. To further allay Western fears, Hu recently began a series of clinical trials and extensive research on stem cells, which he hopes to publish in the usual journals in the West.

Worrisome turning point

Kremer declares that he has never considered treatment at one of the clinics abroad because they “are done by charlatans, who exploit the despair of the patients.” It’s difficult to estimate the number of Israelis who have agreed to try stem cell treatment in those clinics, because they are not required to report the trip to any organization. But conversations with doctors, researchers and patients indicate that the numbers are quite small, certainly compared to the United States or European countries. Here it seems to be a few dozen. Still, one case of an Israeli patient who traveled to Moscow for stem cell treatment managed to arouse reactions in the media, caused an uproar in the medical community and even influenced trade on the stock exchange.

In 2005, a 9-year-old Israeli boy who was suffering from ataxia telangiectasia – a rare genetic disease that causes motor difficulties and problems in the immune system – traveled to a stem cell clinic in Moscow. He underwent treatment and returned to Israel without any evident improvement in his condition. Four and a half years after the treatment, he began to suffer from pressure in his spine. He was treated at Sheba Medical Center, where doctors found that the source of the pressure was a tumor in his spine near the place where the stem cells had been injected.

“We discovered that the tumor had been created from foreign cells, which originated not in the body of the patient himself, but in stem cells that had been implanted in him,” says Dr. Amariglio.

Amariglio’s laboratory began to study the case thoroughly. In 2009 she and her colleagues published an article in the scientific journal PLOS Medicine ‏(published by the Public Library of Science‏) that caused a sensation. According to the study, among their many characteristics, stem cells also contain a cancerous distribution mechanism, and therefore treatment with them is liable to be dangerous.

The report was not easy to digest for the scientists who invest their energy in research, and the many investors who put money into it. Many firms involved in such research, including BrainStorm, are traded on the stock exchange, and the article’s publication led to a decline in the value of their shares ‏(although the value of BrainStorm shares has risen‏ since then).

Amariglio says it was difficult to publish the study, because it was clear that it would make waves and damage a widespread industry. “There’s magic in the subject of stem cells as a medical treatment; that’s why the scientific journals were afraid to publish the article,” she says. But from the moment it came out, it has already been cited in over 300 other articles and research studies.

Prof. Or is not upset by the findings of Amariglio and her colleagues. He explains that medical history is full of tough beginnings. “The first operations to repair coronary arteries of the heart involved complications, but that didn’t stop its development and today there are impressive successes in the field.” Kremer shares Or’s optimism, and is convinced that the medical solution to many diseases, including ALS, lies with stem cells. “Thanks to my activity in Prize4Life, I constantly have my finger on the pulse of what is happening today in medical research. From what I see and understand, stem cells have tremendous potential. Apparently I’m not the only one who thinks so, if they chose to award the Nobel Prize this year to stem cell researchers.”

Religious differences

When they are used in scientific research, most stem cells come from animals, but when it comes to medicine, they must have a human source − which is divided into two main groups, adult and fetal stem cells. Stem cells from an adult are at the heart of the consensus and no one sees anything unethical about producing them. Treatment with them is already common today − in bone marrow transplants for leukemia patients, for example. The ethical and religious questions arise with fetal stem cells that originate in a fertilized egg that has never reached the uterus. A fertilized egg is an excellent source of stem cells, which divide quickly and are relatively easy to produce. That is why they are attractive for research, but controversial in religious terms, because, theoretically, if that same egg were to reach some uterus, it could have developed into a baby.

The idea that scientific use is being made of an entity with the potential to become a fetus is not easily accepted in the Christian world. In 2006, eight European Union countries, most of them Catholic, opposed the funding of stem cell research ‏(25 countries supported it, and the funding ultimately continued). In the United States, too, the dispute reached its height that same year, when then President George W. Bush cast a veto against research with fetal stem cells. That was the first time in his tenure when he had used his right to cast a veto. That brought an end to federal funding, and, with it, progress in research in the field in the United States. The research resumed after the incumbent president, Barack Obama, reversed the decision and allowed the funding to resume.

In Judaism and Islam, a fetus is not considered the same as a person, and there is no opposition to using fertilized eggs for lifesaving research. Israeli law, as well as the religious establishment, permit producing stem cells from a fertilized egg that has not yet been implanted in the uterus. The ethical approval is joined by the widespread fertility treatment industry in Israel, which contributes the raw materials for the research. This had led to the flourishing of stem cell research in Israel and its place at the forefront of world efforts. Israel has the largest number of articles, patents and studies relating to stem cells, per capita, in the world.

Stem cells that became neurons in the cochlea of a deaf gerbil in a laboratory of the University of Sheffield in England. Credit: Reuters
Types of clinical trials with stem cells in 2010Credit: Future medicine
A BrainStorm stem cell laboratory in Jerusalem. Trying to conquer ALS. Credit: Nir Kafri
Patients in stem cell clinics worldwide, in thousands.Credit: Future Medicine
Prof. Daniel Offen. “There is a large gap between Western standards and those in the rest of the world.”

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