Immortal cells of henrietta lax. The Immortal Life of Henrietta Lux Immortal Woman's Cell Culture Nela

We discussed something with you, but look at what interesting information I just found on this one.

Laboratory-grown human cell cultures are often used in biomedical research and in the development of new treatments. Among the many cell lines, one of the most famous is HeLa. These cells, imitating the human body in vitro (“in vitro”), are “eternal” - they can endlessly divide, the results of research using them are reliably reproduced in different laboratories. On their surface, they carry a fairly universal set of receptors, which allows them to be used to study the action of various substances, from simple inorganic to proteins and nucleic acids; they are unpretentious in cultivation and tolerate freezing and conservation well.

These cells got into big science quite unexpectedly. They were taken from a woman named HEnrietta LAcks, who died shortly thereafter. But the cell culture of the tumor that killed her turned out to be an indispensable tool for scientists.

Let's find out more about this ...

Henrietta Lacks

Henrietta Lacks was a beautiful black American woman. She lived in the small town of Turner in South Virginia with her husband and five children. On February 1, 1951, Henrietta went to Johns Hopkins Hospital - she was worried about the strange discharge that she periodically found on her underwear. The medical diagnosis was terrible and merciless - cervical cancer. Eight months later, despite surgery and radiation therapy, she died. She was 31 years old.

While Henrietta was in Hopkins Hospital, the attending physician sent the tumor cells obtained by means of a biopsy for analysis to George Gay, the head of the tissue cell research laboratory at Hopkins Hospital. At that time, the cultivation of cells outside the body was only at the stage of formation, and the main problem was the inevitable cell death - after a certain number of divisions, the entire cell line died.

It turned out that cells designated "HeLa" (an acronym for Henrietta Lax's first and last name) multiplied much faster than cells from normal tissues. In addition, the malignant transformation made these cells immortal - their growth suppression program was turned off after a certain number of divisions. This has never happened in vitro with any other cell. This opened up unprecedented perspectives in biology.

Indeed, never before that moment could researchers consider the results obtained in cell cultures completely reliable: all experiments were carried out on dissimilar cell lines, which eventually died - sometimes even before they could get any results. And then the scientists became the owners of the first stable and even eternal (!) Cell line, which adequately mimics the properties of the organism. And when it was discovered that HeLa cells could even survive mailing, Gay sent them out to his colleagues across the country. Very soon, the demand for HeLa cells grew and they were replicated in laboratories around the world. They became the first "template" cell line.

It so happened that Henrietta died on the very day when George Gay spoke in front of television cameras, holding a test tube with her cells in his hands. He stated that an era of new perspectives in drug discovery and biomedical research has begun.

Why are her cells so important?

And he was right. The cell line, identical in all laboratories of the world, made it possible to quickly obtain and independently confirm more and more new data. We can safely say that the giant leap in molecular biology at the end of the last century was due to the ability to cultivate cells in vitro. Henrietta Lacks' cells were the first immortal human cells ever grown in artificial culture media. HeLa trained researchers to cultivate hundreds of other cancer cell lines. And although in recent years the priority in this area has shifted towards cell cultures of normal tissues and induced pluripotent stem cells (Japanese scientist Shinya Yamanaka received the Nobel Prize in Physiology or Medicine 2012 for the discovery of a method for returning cells of an adult organism to an embryonic state), nevertheless cancer cells remain the accepted standard in biomedical research. The main advantage of HeLa is uncontrollable growth on simple nutrient media, which allows large-scale research at a minimum cost.

Since the death of Henrietta Lacks, her tumor cells have been continuously used to study the molecular patterns of the development of a variety of diseases, including cancer and AIDS, to study the effects of radiation and toxic substances, to draw up genetic maps and a huge number of other scientific problems. In the biomedical world, HeLa cells have become as famous as laboratory rats and petri dishes. In December 1960, HeLa cells were the first to fly into space in a Soviet satellite. Even today, the scope of the experiments carried out then by Soviet geneticists in space is striking. The results showed that HeLa do well not only in terrestrial conditions, but also in zero gravity.

Without HeLa cells, the development of the polio vaccine developed by Jonas Salk would have been impossible. By the way, Salk was so confident in the safety of the vaccine he received (weakened polio virus) that, to prove the reliability of his medicine, he injected himself, his wife and three children.

Since then, HeLa has been used for cloning (preliminary experiments on transplanting cell nuclei before cloning the famous Dolly sheep were carried out on HeLa), for testing methods of artificial insemination and thousands of other studies (some of them are shown in the table).

Besides science ...

The personality of Henrietta Lacks herself was not advertised for a long time. For Dr. Gay, of course, the origin of HeLa cells was no secret, but he believed that privacy was a priority, and for many years the Lax family did not know that Henrietta's cells were famous throughout the world. The mystery was revealed only after the death of Dr. Gay in 1970.

Recall that the standards of sterility and techniques for working with cell lines were in their infancy at that time, and some errors surfaced only years later. So in the case of HeLa cells - after 25 years, scientists found that many of the cell cultures used in research, originating from other types of tissues, including breast and prostate cancer cells, were infected with the more aggressive and tenacious HeLa cells. It turned out that HeLa can move with dust particles in the air or on insufficiently washed hands and take root in cultures of other cells. This caused a big scandal. Hoping to solve the problem by genotyping (sequencing - a complete reading of the genome - at the time was still only planned as a grandiose international project), one group of scientists tracked down Henrietta's relatives and asked for DNA samples from the family in order to map the genes. Thus, the secret became apparent.

By the way, the Americans are still more worried about the fact that Henrietta's family did not receive compensation for using HeLa cells without the consent of the donor. To this day, the family lives in not very good prosperity, and financial assistance would be very useful. But all requests run into a blank wall - there have been no respondents for a long time, and the Medical Academy and other scientific structures predictably do not want to discuss this topic.

On March 11, 2013, a new publication added fuel to the fire, where the results of the complete genome sequence of the HeLa cell line were presented. Again, the experiment was carried out without the consent of Henrietta's descendants, and after some ethical controversy, full access to genomic information was only allowed to professionals. Nevertheless, the complete genomic sequence of HeLa is of great importance for subsequent work, allowing the use of the cell line in future genomic projects.

Real immortality?

The malignant tumor that killed Henrietta made her cells potentially immortal. Did this woman want immortality? And did she get it? If you think about it, a fantastic sensation arises - a part of a living person, artificially multiplied, endures millions of tests, “tastes” all drugs before they are tested on animals, is racked to the ground by molecular biologists all over the world ...

Of course, none of this has anything to do with "life after life." It is foolish to believe that in the cells of HeLa, constantly tormented by insatiable scientists, there is at least some part of the soul of an unhappy young woman. Moreover, these cells can be considered human only in part. In the nucleus of each HeLa cell, there are 76 to 82 chromosomes due to the transformation that occurred during malignancy (normal human cells contain 46 chromosomes), and this polyploidy periodically raises debates about the suitability of HeLa cells as a model of human physiology. It was even proposed to isolate these cells into a separate, close to human species, called Helacyton gartleri, in honor of Stanley Gartler, who studied these cells, but this is not seriously discussed today.

However, researchers are always mindful of the limitations that need to be borne in mind. First, HeLa, despite all the changes, still remains human cells: all their genes and biological molecules correspond to human ones, and molecular interactions in the overwhelming majority of cases are identical to the biochemical pathways of healthy cells. Secondly, polyploidy makes this line more convenient for genomic studies, since the amount of genetic material in one cell is increased, and the results are clearer and more contrasting. Thirdly, the wide distribution of cell lines around the world allows you to easily repeat the experiments of colleagues and use the published data as a basis for your own research. Having established the basic facts on the HeLa model (and everyone remembers that this is even a convenient, but only a model of the organism), scientists are trying to repeat them on more adequate model systems. As you can see, HeLa and similar cells represent the foundation for all science today. And, despite the ethical and moral disputes, today I want to honor the memory of this woman, because her involuntary contribution to medicine is invaluable: the cells left after her saved and continue to save more lives than any doctor can do.

Cellular record holders

The immortality of HeLa cells is associated with the consequences of infection with the human papillomavirus HPV18. The infection caused triplodia of many chromosomes (the formation of three copies of them instead of the usual pair) and the splitting of some of them into fragments. In addition, the infection increased the activity of a number of cell growth regulators, such as the genes telomerase (a regulator of cell death) and c-Myc (a regulator of the activity of the synthesis of many proteins). These unique (and random) changes made HeLa cells the record for growth rate and resistance, even among other cancer cell lines, of which there are several hundred today. In addition, the obtained changes in the genome turned out to be very stable and in laboratory conditions remain unchanged over all the past years.

Here is a chapter from Rebecca Sklut's The Immortal Life of Henrietta Lacks

Soon after Henrietta's death, the HeLa factory began to be created, a large-scale enterprise that would make it possible to grow trillions of HeLa cells every week. The factory was built for one single reason - to stop polio.

By the end of 1951, the world's largest polio epidemic in history. Schools were closed, parents were in a panic. A vaccine was urgently needed. In February 1952, Jonas Salk of the University of Pittsburgh announced that he had developed the world's first polio vaccine, but could not offer it to children until he had thoroughly tested its safety and effectiveness. This required cultured cells in such huge industrial volumes in which they had never been produced before.

The National Endowment for Infant Paralysis (NFIP), a charity founded by President Franklin Delano Roosevelt, who was himself paralyzed by polio, was preparing the largest field trial of a polio vaccine in medical history. It was planned that Salk would vaccinate two million children, and the NFIP would take blood from them to test if they were immune. However, millions of neutralization tests will have to be carried out when the serum of vaccinated children is mixed with live polio viruses and cultured cells. If the vaccine works, then the serum of the vaccinated children should block the polio virus and protect the cells. Otherwise, the virus infects cells and causes damage that scientists can see under a microscope.

The difficulty was that monkey cells were used for neutralization tests, which died during this reaction. This was a problem - not because they took care of the animals (this was not discussed then, unlike in our time), but because the monkeys were expensive. Millions of neutralization reactions with monkey cells would cost millions of dollars, so the NFIP frantically looked for a cell to culture that could multiply en masse and cost less than monkey cells.

The NFIP turned to Guy and several other cell culture specialists for help, and Guy realized that this was truly a gold mine. As a result of the charity, the NFIP received an average of $ 50 million annually in donations, and his director wanted to donate most of this amount to cell cultivators so that they could find the way to mass-produce cells that everyone has dreamed of for many years.

The offer came at the right time: by a happy coincidence, shortly after the call from the NFIP asking for help, Guy realized that Henrietta's cells did not grow like any human cells he had met so far.

Most cells in culture grow in a single layer in the form of a clot on the surface of the glass, which means that the free space quickly runs out. Increasing the number of cells is labor intensive: Scientists have to scrape the cells out of the test tube again and again and distribute them in several new containers to give the cells new space to grow. As it turned out, HeLa cells are very unpretentious: they did not need a glass surface to grow, they could grow by floating in a culture medium that was constantly stirred by a "magic device" - an important technology developed by Guy, today it is called suspension cultivation. This meant that HeLa cells were not limited by space like everyone else; they could share as long as the culture medium remained. The larger the container with the culture medium, the more cells grew. The discovery meant that if HeLa cells are susceptible to the polio virus (because some cells are insensitive to it), it would solve the problem of mass cell production and help avoid testing the vaccine on millions of monkey cells.

And so in April 1952, Guy and his colleague on the NFIP Advisory Committee, William Scherer - a young researcher at the University of Minnesota who recently defended his thesis - tried to infect Henrietta's cells with the polio virus. A few days later, they discovered that HeLa was actually more susceptible to the virus than any other cultured cells so far. And they realized that they had found exactly what the NFIP needed.

They also realized that before they could start mass-producing any cells, they needed to find a new way to transport them. The airplane drop-off that Guy used was great for sending multiple vials to colleagues, but too costly for large volumes. Billions of cells grown will be useless if those cells cannot be delivered to the right place. And scientists started experimenting.

In 1952, on Memorial Day, Guy took several tubes of HeLa and enough culture medium to last several days for the cells to live, and placed them in a tin container lined with a cork and filled with ice to avoid overheating. Providing all this with detailed care instructions, he sent Mary to the post office to send a parcel with test tubes to Scherer in Minnesota. Due to the holiday, all post offices in Baltimore were closed, except for the central office in the downtown area. To get there, Mary had to change several trams, but in the end she got there. So did the cages: four days later, the package arrived in Minneapolis. Scherer placed the cells in an incubator and began to grow. For the first time, living cells have successfully postponed dispatch.

In the months that followed, to make sure the cells could withstand the long journey in any climate, Guy and Scherer sent HeLa tubes by plane, train, and truck across the country, from Minneapolis to Norwich, New York, and back. The cells died in only one test tube.

When the NFIP learned that HeLa was susceptible to the polio virus and could be grown in large quantities at low cost, an agreement was immediately made with William Scherer to oversee the development of the HeLa Distribution Center at Tuskegee University, one of the country's most prestigious universities for black. The NFIP chose Tuskegee University for this project because of Charles Bynum, director of the foundation's Negro Activities. Bynum - a science teacher and civil rights activist and the nation's first black foundation director - wanted to host the center in Tuskegee for hundreds of thousands of dollars in funding, many jobs, and training opportunities for young black scientists.

Within a few months, a team of six black scientists and laboratory technicians had built a factory in Tuskegee never seen before: industrial steel autoclaves for steam sterilization lined the walls, huge vats of mechanically stirred culture medium stood in rows, incubators full of glass bottles for cell cultures, and automatic cell dispensers - tall, with long, thin metal handles that inject HeLa cells into one tube after another. Each week, the team in Tuskegee prepared thousands of liters of Guy's recipe culture medium, mixing salts, minerals and blood serum from the scores of students, soldiers and cotton farmers who responded to advertisements in the local newspaper for donating blood for money.

Several technicians served as a quality control pipeline and viewed hundreds of thousands of HeLa cell cultures every week to ensure they were viable and healthy. Others sent cells to researchers across the country on a strict schedule at 23 polio vaccine testing centers.

Ultimately, the Tuskegee team grew to 35 scientists and lab technicians who produced 20,000 HeLa tubes a week - about 6 trillion cells. It was the very first cell factory, and started with a single HeLa tube that Guy sent to Scherer in his first test package shortly after Henrietta's death.

Using these cells, scientists were able to prove the effectiveness of the Salk vaccine. Soon in New York Times there were photographs of black women bent over microscopes, examining cells and holding test tubes with HeLa in their black hands. The headline read:

DEPARTMENT IN TASKIGI HELPS TO FIGHT POLIOMYELITIS
The Negro Scientist Team Plays a Key Role
in the development of Dr. Salk's vaccine
HELA CELLS GROW

Black scientists and laboratory technicians, many of them women, used the cells of a black woman to save the lives of millions of Americans - most of whom were white. And it happened at the same university and at the same time that government officials were conducting the infamous syphilis study.

Initially, the Tuskegee center only supplied HeLa cells to laboratories that tested polio vaccines. However, when it became clear that there were enough HeLa cells for everyone, they began to be sent to all scientists who were ready to purchase them for ten dollars plus the cost of airmail. If scientists wanted to find out how cells would behave in a particular environment, how they would react to a certain chemical, or how they build a certain protein, they turned to HeLa cells. Although they were cancerous, they had all the fundamental characteristics of normal cells: they built protein and communicated with each other like normal cells, dividing and producing energy, ferrying and regulating genetic material, and were susceptible to infections, which made them an optimal tool. to synthesize and study everything that is possible - including bacteria, hormones, proteins and especially viruses.

Viruses multiply by "injecting" particles of their genetic material into a living cell. The cell radically changes its program and begins to reproduce the virus instead of itself. When it came to growing viruses, as in many other cases, the malignant nature of HeLa only made them more useful. HeLa cells grew much faster than normal cells and therefore brought results faster. HeLa cells were the workhorse — hardy, inexpensive, and ubiquitous.

The timing was right. In the early 1950s, scientists were just beginning to understand the nature of viruses, and when Henrietta's cells appeared in laboratories around the country, researchers began to infect them with all kinds of viruses - herpes, measles, mumps, chickenpox, equine encephalitis - to study how the virus penetrates into cells, multiplies in them and spreads.

Henrietta's cells helped lay the foundations of virology, but that was just the beginning. In the first years after Henrietta's death, having received the first test tubes with her cells, researchers around the world were able to make several important scientific discoveries. First, a team of scientists used HeLa to develop methods for freezing cells without damaging or altering them. Thanks to these methods, cells began to be shipped around the world in a proven and standardized way that was used to transport frozen food and frozen semen for livestock production. It also meant that scientists could keep cells in between experiments without worrying about nutrition and sterility. However, most of all scientists were pleased with the fact that freezing made it possible to "fix" cells in their most varied states.

The cell was frozen like pressing the "pause" button: division, metabolism and all other processes stopped and resumed after defrosting, as if you simply pressed the "start" button. Scientists could now pause the development of cells at any frequency during the experiment, in order to compare the response of certain cells to a drug after one, two or six weeks. They could observe the state of the same cells at different periods of development: scientists hoped to see at what point a normal cell growing in culture becomes malignant - a phenomenon called spontaneous transformation.

Freezing is the first in a list of amazing improvements in tissue culture thanks to HeLa. Another breakthrough was the standardization of the cell culture process, an area that had been a mess until then. Guy and his colleagues complained that they spend too much time preparing the culture medium and keeping the cells alive. What worried them most, however, was that because everyone used different ingredients to formulate the culture medium, different recipes, different cells and different techniques, and few knew about their colleagues' methods, it was difficult or nearly impossible to replicate anyone’s experiment. And repetition is a necessary part of science: a discovery is not considered valid if others cannot repeat and get the same results. Guy and others feared that tissue culture could stagnate without standardizing methods and materials.

For a long time, scientists believed that human cells contain forty-eight chromosomes - strands of DNA inside cells, which contain all of our genetic information. However, the chromosomes stuck together, and it was not possible to accurately count them. In 1953, a Texas geneticist mistakenly mixed the wrong liquid with HeLa and some other cells. This accident turned out to be a happy one. The chromosomes in the cells swelled and separated from each other, and for the first time scientists were able to examine each of them in detail. This accidental discovery was the first in a string of discoveries that allowed two researchers in Spain and Sweden to discover that a normal human cell contains forty-six chromosomes.

Now knowing how many chromosomes must to have a person, scientists could say that someone has more or less of them, and with the help of this information, diagnose genetic diseases. Soon enough, researchers around the world began to identify chromosomal abnormalities. So, it was found that patients with Down syndrome had an additional chromosome in the twenty-first pair, those suffering from Klinefelter's syndrome had an extra sex x-chromosome, and in patients with Shereshevsky-Turner syndrome, this chromosome was absent or was defective.

With all these new developments, the demand for HeLa cells increased and the Tuskegee center was no longer able to meet it. The owner of Microbiological Associates - a military man named Samuel Reeder - was not knowledgeable, but his business partner Monroe Vincent was himself a researcher and understood how big the potential market for cells was. Cells were required by many scientists, and few of them had the time or the ability to grow them in sufficient quantities on their own. The researchers just wanted to buy the cells, so Reeder and Vincent decided to use HeLa as a springboard to launch the first industrial commercial center for the supply of cells.

It all started with a cell factory - as Reeder called it. In Bethesda, Maryland, in the midst of a spacious warehouse that was once a factory for making Fritos chips, he erected a glass enclosure and a moving conveyor belt with hundreds of built-in test tube racks. Outside the glass room, everything was organized almost like in Tuskegee - huge vats of culture medium, only even larger. When the cages were ready for shipment, a loud bell rang and all the factory workers, including the mailing department employees, interrupted current business, washed properly in the sterilization room, put on a robe and cap, and lined up at the conveyor belt. Some filled the test tubes, others closed them with rubber stoppers, sealed them or placed them in a portable incubator, where they were stored until packaging for shipment.

Laboratories like the National Institutes of Health were Microbiological Associates' largest customers, and they continually ordered millions of HeLa cells on a set schedule. However, scientists from anywhere in the world could place an order, pay less than fifty dollars, and Microbiological Associates immediately sent them tubes of HeLa cells. Reader signed an agreement with several major airlines, and therefore, wherever the order came from, the courier sent the cells on the next flight, they were picked up at the airport and delivered to the laboratories by taxi. This is how the multi-billion dollar industry of human biomaterials was born step by step.

Henrietta's cells could not restore youthfulness to women's necks, but cosmetic and pharmaceutical companies in Europe and the United States began to use them instead of laboratory animals to test new products and drugs that caused cell destruction or damage. Scientists cut HeLa cells in half, and proved that cells can live after removing the nucleus, they used them to develop methods of injecting substances into the cell without killing it. HeLa was used to understand the effects of steroids, drug chemotherapy, hormones, vitamins, and environmental stress; they were infected with tuberculosis, salmonella and the bacteria that cause vaginitis.

In 1953, at the request of the US government, Guy took Henrietta's cells with him to the Far East to study the hemorrhagic fever that was killing American soldiers. He would inject HeLa into rats and see if they got cancer. For the most part, however, he was trying to move from HeLa to growing normal and cancer cells from one patient in order to compare them with each other. He could not escape the seemingly endless questions about HeLa and cell culture from other scientists. Every week, scientists repeatedly visited his laboratory with requests to teach them the technique, and he often had to travel around the world, helping to establish work on cell multiplication.

Many of Guy's colleagues insisted that he publish the research data and receive the recognition it deserves, but he was always discouraged from being busy. He worked at home all night long. He was late with the deadline for preparing documents for the grant, often delayed for months with replies to letters, and once paid the salary of a deceased employee for three months before someone noticed it. Mary and Margaret grumbled for a year to get George to publish anything about growing HeLa; he ended up writing a short paragraph for the conference. After that, Margaret herself wrote about his work in his place and fussed about publication.

By the mid-1950s, many scientists were already working with cell cultures, and Guy was tired. He wrote to friends and colleagues: "Someone has to figure out how to call what is happening now, say, 'The world has gone crazy with this growing of fabrics and its possibilities." I hope that at least some of this chatter about tissue cultivation has a foundation and benefits people ... and most of all I want this hype to subside a little ... "

Guy was annoyed by the hype around HeLa. After all, there were other cells, including those he himself had grown: A.Fi. and D-1 Re, named for the patients from whom the original sample was taken. Guy offered them to scientists all the time, but these cells were more difficult to grow and therefore they were never as popular as Henrietta's cells. Guy no longer distributed HeLa as the companies took over the task, however he did not like the fact that HeLa cultivation was completely out of his control.

Ever since the Tuskegee manufacturing plant went into operation, Guy has been sending letters to scientists in an attempt to limit the uses of HeLa cells. He once complained in a letter to his old friend Charles Pomerat that everyone around, including the staff of Pomerat's laboratory, used HeLa for research, which Guy was "more capable" of, and some had already been done, but had not yet published the results ... Pomerat wrote in response:

As for your… disapproval of the widespread study of the HeLa strain, I don’t understand how you can hope to slow things down, for you yourself have spread this strain so widely that it can now be purchased for money. This is almost the same as asking people not to experiment on golden hamsters! .. I understand that it was only thanks to your kindness that HeLa cells became available to the public. Therefore, why, in fact, now you think that everyone wants to grab a piece for themselves?

Pomerat believed that Guy should have completed his own research on HeLa before "releasing it to the general public, for after that culture becomes a universal scientific property."

However, Guy did not. As soon as HeLa cells became "universal scientific property", people began to wonder who was their donor.

The original article is on the site InfoGlaz.rf The link to the article this copy was made from is

MOSCOW, August 7 - RIA Novosti. The decoding of the genome of HeLa "immortal" cancer cells, which researchers use to study a variety of diseases and test drugs, caused a scandal when the decryption was published in the public domain, according to an article published in the journal Nature.

This story could lead to changes in American legislation and make the conditions for the use of human biological tissues in scientific research more stringent, the authors of the publication believe.

Immortal cells

In 1951, doctors at Johns Hopkins Hospital in Baltimore (Maryland, USA) took a tumor sample from Henrietta Lacks, an African-American woman with cervical cancer. Lax died of cancer, and her cells gave rise to the first "immortal" human cell line, known as HeLa. Until then, all attempts to grow human cells in culture ended in their death, and HeLa continues to live to this day.

These cells became the "testing ground" for numerous studies around the world, which began with the trial of a polio vaccine. They are used to study cancer, AIDS and many other diseases, as well as the effects of radiation and toxic substances on human cells. In 1960, HeLa went into space on a Soviet satellite. Nowadays, they can be found in about 74 thousand scientific articles.

Decoding the Hela genome

In 2013, two groups of scientists decoded the genome of "immortal" cells. This was first done by German researchers led by Lars Steinmetz of the European Laboratory for Molecular Biology in Heidelberg, Germany. After analyzing the data obtained, they found that the HeLa genome differs significantly from the genome of ordinary human cells: they contain many mutations, extra copies of genes and rearrangements. This is partly due to the fact that HeLa cells are cancerous, and some of the changes have accumulated over the years of cultivation in the laboratory.

US Supreme Court has banned patenting of the human genomeNaturally occurring DNA is "a product of nature and cannot be patented because it was isolated," the court said.

Then a research team from the University of Washington in Seattle (USA) led by Jay Shendure also deciphered the HeLa genome and found the reason why Lax developed cancer. They studied the incorporation of human papillomavirus genes into the HeLa genome. This virus itself carries a set of genes that contribute to the development of cancer, in addition, it is inserted next to an oncogene, mutations in which lead to the development of cancerous tumors. Scientists believe that the proximity of the papillomavirus genes to the oncogene was the reason for the development of a very aggressive form of cancer in Lax.

"This is probably the worst case for how the papillomavirus could have inserted itself into her genome," explained co-author Andrew Adey of the University of Washington.

Research without permission

In the middle of the 20th century, scientists did not need permission from Henrietta herself or her relatives to use cells in research. Therefore, for a long time, members of the Lax family did not suspect what role Henrietta's cells played in the development of science. However, upon learning about the use of HeLa cells in research, her relatives were outraged that all this was happening without their knowledge.

The topic received a new round of development in March 2012, when Steinmetz and his colleagues uploaded the decoding of the HeLa cell genome to databases available to the scientific community.

The results of decoding the genomes of ordinary people cannot be published along with their personal data. But in the case of HeLa, scientists did not violate any laws and did not see anything reprehensible in this: these cells have long become a familiar object of research. However, the Lacks family was outraged. Despite the differences between HeLa and healthy human cells, they can reveal some hereditary traits of the family. The genome decryption was removed from the databases, but this did not solve the problem.

The results of a study of the genome of HeLa cells, carried out by Shendur's group, were accepted for publication in the journal Nature. This implies the mandatory publication of research data. The problem of confidentiality of decoding the HeLa genome has become urgent again.

To find a way out of this situation, Francis Collins, the director, and Kathy Hudson, the deputy director of the US National Institutes of Health met with representatives of the Lacks family. Together they decided to publish the decoding of the HeLa genome, restricting access to it. Scientists who wish to review this data will have to contact the National Institutes of Health, where their request will be reviewed, including by representatives of the Lax family. Thus, Lacks will know who is using this data and for what purposes, and will be able to determine the terms of their use. Shendur's study was the first to be published with the consent of the Lacks.

Of course, there remains the possibility to restore the HeLa genome from the data published over the years of cell research, or to decipher it anew and put it back on the Internet. The US National Institutes of Health will not be able to influence those researchers, whose work it does not fund, write the leaders of the institute in the same issue of Nature, where Shendur's study was published. However, they called on the scientific community to respect the rights of the Lax family.

Changes in legislation

This case is unique, the leadership of the National Institutes of Health emphasizes, and therefore is considered on an individual basis. However, he drew public attention to the conditions for the use of biological samples in scientific research.

The current US laws leave it possible to obtain a complete decoding of the human genome on the basis of such a sample without his knowledge. The only limitation is that the sample must be anonymous. However, in the age of computer processing, such protection is very conditional, the leadership of the National Institutes of Health admits.

"In addition, the relationship between scientists and research participants is evolving: the permission request emphasizes that the participants are partners (scientists) and not just a subject of study," Collins and Hudson write.

Now the leadership of the National Institutes of Health is preparing proposals for amendments to American laws. If these changes are adopted, scientists will have to obtain permission from the "donors" of biological tissues to use the material, regardless of the anonymity of the study.

Laboratory-grown human cell cultures are often used in biomedical research and in the development of new treatments. Among the many cell lines, one of the most famous is HeLa - endothelial cells of the uterus. These cells, imitating a simplified "person" in laboratory research, are "eternal" - they can endlessly divide, endure for decades in the freezer, and can be divided into parts in different proportions. On their surface, they carry a fairly universal set of receptors, which allows them to be used to study the action of various cytokines; they are not very whimsical in cultivation; they tolerate freezing and preservation very well. These cells got into big science quite unexpectedly. They were taken from a woman named Henrietta Lacks, who died shortly thereafter. Let's consider the whole story in more detail.

Henrietta Lacks

Figure 1. Henrietta Lacks with her husband David.

Henrietta Lacks was a beautiful black American woman. She lived in the small town of Turner, South Virginia with her husband and five children. On February 1, 1951, Henrietta Lacks went to the Johns Hopkins Hospital - she was worried about the strange discharge that she periodically found on her underwear. The medical diagnosis was terrible and merciless - cervical cancer. Eight months later, despite surgery and radiation exposure, she died. She was 31 years old.

While Henrietta was at Hopkins Hospital, the attending physician sent her tumor (cervical biopsy) for analysis to George Gay ( George gey) - Head of the Tissue Cell Research Laboratory at Hopkins Hospital. Recall that at that time the cultivation of cells outside the body was only at the stage of formation, and the main problem was the predetermined death of cells - after a certain number of divisions, the entire cell line died.

It turned out that cells designated "HeLa" (an acronym for the first and last name Henrietta Lacks) multiplied twice as fast as cells from normal tissues. This has never happened to any other cell before. in vitro... In addition, the transformation made these cells immortal - their growth suppression program was turned off after a certain number of divisions. This opened up unprecedented perspectives in biology.

Indeed, never before that moment could researchers consider the results obtained in cell cultures so reliable: previously, all experiments were carried out on dissimilar cell lines, which eventually died - sometimes before they could get any results. And then scientists got the first stable and even eternal(!) a cell line that adequately mimics the essence of the organism. And when it was discovered that HeLa cells could even survive mailing, Gay sent them out to his colleagues across the country. Very soon, the demand for HeLa cells grew and they were replicated in laboratories around the world. They became the first "template" cell line.

It so happened that Henrietta died on the very day when George Gay spoke in front of television cameras, holding a test tube with its cells in his hands, and declared that a new era in medical research began - an era of new perspectives in the search for drugs and the study of life.

Why are her cells so important?

And he was right. The cell line, identical in all laboratories of the world, made it possible to quickly obtain and independently confirm more and more new data. We can safely say that the giant leap in molecular biology at the end of the last century was due to the ability to cultivate cells in vitro... Henrietta Lacks' cells were the first immortal human cells ever grown in artificial culture media. HeLa has trained scientists to cultivate hundreds of other cancer cell lines. And, although conditions for the cultivation of untransformed cells have not yet been found, cancer cells for the most part are an adequate model for finding answers to questions asked by scientists and doctors.

Without HeLa cells, the development of the polio vaccine developed by Jonas Salk ( Jonas Salk). By the way, Salk was so confident in the safety of the vaccine he received (weakened polio virus) that, to prove the reliability of his medicine, he first injected himself, his wife and three children with the vaccine.

Since the death of Henrietta Lacks, her tumor cells have been continuously used to research diseases such as cancer, AIDS, to study the effects of radiation and toxic substances, to draw up genetic maps and a huge number of other scientific problems. In the biomedical world, HeLa cells have become as famous as laboratory rats and petri dishes. In December 1960, HeLa cells were the first to fly into space in a Soviet satellite. By the way, even today the scope of experiments carried out by then Soviet geneticists in space is striking (see sidebar).

The results showed that HeLa do well not only in terrestrial conditions, but also in zero gravity. Since then, HeLa has been used for cloning (preliminary experiments on nuclear transplantation before cloning the famous Dolly sheep were carried out on HeLa), and for compiling genetic maps, and for practicing artificial insemination, and thousands of other studies (see Figure 2).

Space genetics in the USSR

On the third spaceship-satellite (12/01/1960) even more living objects went into flight: two dogs - Bee and Mushka, two guinea pigs, two white laboratory rats, 14 black C57 mice, seven hybrid mice from SBA mice and C57 and five white outbred mice. There were also placed six flasks with highly mutable and seven flasks with low-stable Drosophila lines, as well as six flasks with hybrids. In addition, two flasks with flies were covered with additional protection — a 5 g / cm 2 layer of lead. In addition, the ship contained seeds of peas, wheat, corn, buckwheat, horse beans. Seedlings of onion and nigella seeds were flying in a special tray. On board the ship there were several test tubes with actinomycetes, ampoules with human tissue culture in and outside the thermostat, six test tubes with chlorella in a liquid medium. The ebonite cartridges contained sealed ampoules with a bacterial culture of E. coli and two varieties of phage - T3 and T4. Special devices contained HeLa cell culture, human lung amniotic tissue, fibroblasts, rabbit bone marrow cells, as well as a container with frog eggs and sperm. There were also tobacco mosaic viruses of various strains, influenza virus.

From the article by N. Delone "At the origins of cosmic genetics" ("Science and Life", No. 4, 2008).

Beyond science ...

Figure 3. HeLa cells under a scanning microscope in pseudo colors.

Steve Gschmeissner / Science Photo Library

The personality of Henrietta Lacks herself was not advertised for a long time. Dr. Gay, of course, knew about the origin of HeLa cells, but he believed that privacy was a priority, and for many years the Lacks family did not know that it was her cells that became famous throughout the world. After the death of Dr. Gay in 1970, the secret was revealed. It happened in the following way. Recall that the standards of sterility and techniques for working with cell lines were just nascent, and some errors surfaced only years later. So in the case of HeLa cells - after 25 years, scientists found that many cell cultures originating from other types of tissues, including cells of the mammary glands and prostate gland, were infected with more aggressive and tenacious HeLa cells. It turned out that HeLa can move with dust particles in the air or on insufficiently washed hands, and take root in cultures of other cells. This caused a big scandal. In the hope of solving the problem by genotyping (genome sequencing, we recall, was not yet invented), one group of scientists tracked down Henrietta's relatives and asked them to give them samples of the family's DNA in order to map the genes. Thus, the secret became apparent.

By the way, now the Americans are more worried about the fact that Henrietta's family never received compensation for using HeLa cells without the consent of the donor. Plus, to this day, the family lives in not very good prosperity, and financial assistance would be very useful. But all requests run into a blank wall - there have been no respondents for a long time, and the Medical Academy and other scientific structures do not want to keep up the conversation ...

Real immortality?

The malignant tumor that killed Henrietta made her cells potentially immortal. Did this woman want immortality? And did she get it? If we compare the first and last photographs of this article, there is a feeling as in a science fiction novel - a part of a living person, artificially multiplied, endures millions of trials, "tastes" all the drugs before they get to the pharmacy, is there are foundations of molecular biologists all over the world ...

Of course, all this has nothing to do with "life after life." We do not admit that in the HeLa cells, tormented all year round by insatiable graduate students under the laminar of laboratories, there is at least some part of the soul of an unhappy young woman. Nevertheless, I would like to honor the memory of this woman, because her involuntary contribution to medicine is invaluable - the cells left after her have saved and continue to save lives more than any doctor can do.

Literature

  1. Zielinski S. (2010). Henrietta Lacks' immortal cells. Smithsonian Magazine;
  2. Smith V. (2002). Wonder woman. Baltimore city paper.

One of the most amazing and important events in the entire history of medicine and microbiology can rightly be considered the life and death of a seemingly unremarkable African American woman, Henrietta Lacks. She was born in the United States in 1920 to a large family, soon her mother died, and she, along with her nine brothers and sisters, were raised by the same father, who moved the family to his relatives.

Henrietta first became a mother at the age of 12 and gave birth to the first, as well as the next four children from her own cousin. At the age of 14, she married him, already having two children, and for the next fifteen years she lived a completely normal life, of course, adjusted for the rather difficult situation of the African American population in America at that time. During this time, she had three more children, but at the age of 30 she noticed some systematic discharge on her underwear, with which she turned to the Johns Hopkins Hospital.

HeLa cell research

As a result of research, it turned out that Henrietta developed cervical cancer, which was aggravated by the papilloma virus. Not surprisingly, despite all the proposed treatment, Henrietta died after 8 months. However, her story did not end there, quite the opposite. The fact is that even during Henrietta's life, her attending physician transferred part of the cells of her cancerous tumor to the head of the local tissue cell research department, George Guy. And it was he who noted the unique nature of Henrietta's cells because, in fact, they were immortal.

The fact is that ordinary cells of the human body and other living organisms have a certain finite number of divisions, the so-called Hayflick limit. This is due to the fact that in the process of division at the ends of the chromosomes, cells constantly decrease in telomere size until the cell completely loses its ability to divide. The limiting number of divisions is different, however, for most cells of the human body, the maximum is 52 divisions.

At the same time, Henrietta Lacks' cells did not have their Hayflick limit and could divide indefinitely in the nutrient solution. In fact, this is due to the fact that cancerous tumors quite often produce telomerase during their growth, a special enzyme that allows telomeres to constantly maintain their original size and not shrink. Moreover, Henrietta's cells had excellent adaptability to almost any environment and were dividing much faster than most cancer cells. It is also worth noting that cancer cells, later named HeLa (an abbreviation for the donor's name), have an abnormal karyotype, and if the cells of an ordinary person contain 46 chromosomes, then in HeLa cells this number varies from 49 to 78 chromosomes, which in itself is a huge interest for science.

Using immortal cells

Having received such unique cells at his disposal, George Guy quickly realized their potential and began to work on creating conditions for their mass division and development. The fact is that Guy's research department, like many other scientific institutions around the world, has been actively working for more than 10 years to create cell lines, which were required just a huge amount to conduct reliable medical research. However, before the advent of HeLa cells, all efforts were in vain, the Hayflick limit could not be overcome, the process of growing the cells was long, and their transportation became a real problem. At the same time, Henrietta Lacks' cells made it possible to instantly make a real breakthrough in medicine and microbiology, as scientists around the world received an infinite amount of material to work with.

First of all, these cells made it possible to create a vaccine against polio, which was raging in America at that time. At the time of the appearance of HeLa cells, a vaccine against it had already been developed by Jonas Salk, however, without numerous studies, he simply could not use it on living people. Well, since HeLa cells turned out to be much more sensitive to the polio virus, the question of a suitable material was completely resolved.

Of course, the need for a large amount of research material prompted Guy to address the issues of mass production of these cells and their transportation. As it soon became clear, HeLa cells turned out to be very unpretentious to their environment. If ordinary cells can grow only at the junction of the nutrient solution and the air environment, forming a film, then HeLa cells quietly developed in any volume of the nutrient medium, significantly reducing the cost of their production. Moreover, after several tests and attempts, it turned out that the transportation of such cells is not a big problem, because they turned out to be much more resistant and immune to various temperature and other external factors. As a result, HeLa cells began to be transported by mail, while earlier ordinary cells were transported under special conditions on airplanes, since the time factor played a very important role.

HeLa cells exist and are still used today, but since they have been separated many times, there are several branches at once, with different characteristics and features. These cells were used to research cancer, AIDS, dozens of viral diseases, they were used to test a nuclear bomb, they repeatedly went into space, they were inoculated with the genes of living things and plants, infect other cells with them, and did many more important things.

Moreover, Henrietta herself, namely unique cells, even wanted to be isolated as a separate and completely new biological species, due to the abnormal number of chromosomes. And although this initiative was not officially implemented, many researchers adhere to the idea of ​​the completely unique nature of HeLa cells. At the same time, the donor Henrietta himself remained in the shadows for a very long time. She died in 1951, and her doctor considered it a violation of medical secrecy to tell her family about her cell research. The truth was revealed to them much later, when the researchers needed to study all family members, and for many years they tried in vain to get at least some money for the research carried out on their mother's cells.

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